The Most Famous Celebrity Guest Stars On Grey's Anatomy

There's no doubt "Grey's Anatomy," which kicked off its 19th season in 2022, has had a ton of actors come to the show over the years. Most of the original cast as well as some regulars who joined later have become household names thanks to their iconic and memorable characters on "Grey's."

And so, it makes sense a show this popular would attract some seriously big names for their guest spots. The great thing about a show set in a hospital is the need for characters is vast and diverse, spanning all cultures, genders, and age groups. Over the years, the fans have been treated not just to current stars, but classic TV actors and beloved silver screen legends. Whether a guest role was played by a long-established actor or one who appeared before they hit it big in the industry, it's always fun to look back on their performances. 

With literally dozens of actors to choose from, it's even more challenging to narrow down a list. So, who do you think we picked? Keep reading to learn more about the most famous celebrity guest stars on "Grey's Anatomy."

Abigail Breslin

Oscar nominee Abigail Breslin was just 9 years old when "Grey's Anatomy" premiered in 2005, but she already had an impressive start on her acting resume, having begun at the age of 3 in a Toys "R" Us commercial and followed that up with 2002's "Signs" opposite Mel Gibson and Joaquin Phoenix. In 2006, Breslin not only appeared in critical darling "Little Miss Sunshine," for which she received her first Academy Award nom, but she also popped up in a Season 3 episode of "Grey's Anatomy.

Breslin played Megan, a young girl in foster care who came to the ER with numerous cuts and bruises. Dr. Karev, played by Justin Chambers, questions her about the injuries, trying to figure out if the foster parents have been abusing the child. What he discovers, after she ripped out her own staples from a wound on her arm, is that Megan doesn't feel pain. The reason? She tells him she had super powers.

Breslin's performance as the sarcastic and street smart young girl who just wanted her parents to keep her impressed fans. At the time, Entertainment Weekly called her "unforgettable" and said her guest spot was one for the "Grey's Anatomy" Hall of fame, declaring, "Breslin totally raised Justin Chambers' game too, because this was one of Karev's best episodes ever." After that, the young actor practically grew up in front of audiences and has showed up in numerous other TV shows and films like "Definitely, Maybe" and the "Zombieland" franchise.

Demi Lovato

Singer, songwriter, and actor Demi Lovato got her start as one of the kids on "Barney & Friends." She would go on to be a fixture of the Disney Channel, appearing in movies like "Camp Rock" and "Princess Protection Program," as well as playing the titular role in the series "Sonny with a Chance." In 2008, she officially kicked off her music career and released her debut album.

Lovato's character in a Season 6 episode of "Grey's Anatomy" was a struggling young woman named Hayley, whom was believed to be schizophrenic. The role of Hayley was quite a departure from the brighter, more carefree characters she'd played on the Disney Channel. The team ultimately found the cause of her pain: a hole in her inner ear, which had nothing to do with schizophrenia.

Being on "Grey's" was a very big deal to Lovato. Before she filmed her episode, she tweeted (via Parade), "Getting up early tomorrow morning to begin a week of fulfilling one of my biggest dreams." And it sure sounds like it lived up to that dream. As Lovato gushed to RadarOnline, "I got to work with so many talented people and I'm grateful for the entire experience!" What's more, the "Skyscraper" singer won the People's Choice award for Favorite TV Guest Star for her role on "Grey's" and what followed was more acting, more albums, and even three Grammy nominations. 

Alyssa Milano and Holly Marie Combs

In 2019, ABC had a "Cast From the Past" week which placed characters from shows gone by on current ABC shows. Per the ABC website, some of those shows being honored were "Cheers," "Girlfriends," and "Charmed." On one episode of "Grey's Anatomy," "Charmed" stars Alyssa Milano and Holly Marie Combs — two of the three Halliwell sisters — reunited on the small screen.

Combs, who had finished her run on "Pretty Little Liars" two years before, and Milano, who was appearing on "Insatiable," popped up on a Season 16 episode of "Grey's Anatomy." They once again teamed up to play sisters, this time human ones, who come to Pac North — the hospital Richard and Alex were working at —because their sister was braindead after an accident and they have the horrible decision of when to pull the plug.

Krista Vernoff, "Grey's" showrunner, just so happened to also be a writer for "Charmed." Vernoff told People, "Our goal was to wink at 'Charmed' while still making an episode of Grey's Anatomy." And fans definitely got the Halliwell sister vibe with the actors playing off each other's personalities just like Phoebe and Piper had. Then, in an emotional goodbye, the sisters are startled by the phone of their dead sister. When one of them answers, it actually is their sister, whom they believed had just died. Turns out, someone had stolen their sister's bag and the deceased patient in the bed is the thief.

Rachel Brosnahan

Less than five years into her acting career, "The Marvelous Mrs. Maisel" star Rachel Brosnahan snagged a coveted spot on "Grey's Anatomy" in a Season 9 episode. Prior to this, the actor had only appeared in a handful of roles, including guest spots on "Gossip Girl" and "The Good Wife."

In "The Face of Change," Brosnahan played a transgender man who's been saving his money since he was 14 for top surgery.  Brosnahan had some emotional scenes when her character fights with his father, who is not on board with the surgery. For Brosnahan it wasn't just another role; the Emmy winner is also an ally off screen. In 2021, she tweeted, "Hey. Trans women are women and trans men are men. Men and women who need and deserve the same love, respect and support we all rely on to survive and thrive."

And it would seem her performance garnered her the attention she deserved as Brosnahan went on to become a series regular on several shows — "The Black List," "House of Cards," and "Manhattan" — before landing her the starring spot on "The Marvelous Mrs. Maisel," for which she won an Emmy and a Golden Globe.

Tessa Thompson

In Season 2 of "Grey's Anatomy," a young Tessa Thompson appeared in two episodes, playing the teenage niece of Richard Webber. Diagnosed at the age of 14 with ovarian cancer, Camille passed out on prom night while having sex. Thompson's performance rode the line of teenage innocence and being forced into the very adult situation of facing death.

Since those last two episodes were the end of the season, it gave the writers the opportunity to end several dramatic storylines during the course of a "prom night" the hospital put on for Camille, including one that featured Meredith Grey having to decide between her two men. Everyone dresses up and Camille and her uncle Richard are able to have a sweet moment dancing together.

Tessa Thompson went on to secure recurring roles in several series, including "Hidden Palms," "Blue Belle" and "Copper." And it wasn't long before she was in demand as a film actor as well, showing up as strong female characters in such memorable movies like "Dear White People," the "Creed" franchise, and "Thor: Ragnarok," where she got to play superhero Valkyrie. Of her part in "Dear White People," she told Harper's Bazaar, "Never mind what it did for my career, it reaffirmed my faith in filmmaking and the kinds of characters I could play in Hollywood."

Keke Palmer

In 2004, an 11-year-old Keke Palmer made her acting debut opposite Queen Latifah in "Barbershop 2: Back in Business." After that? Her career took off in a big way. Palmer went on to star in films like "Akeelah and the Bee" and "Joyful Noise," as well as lead the Nickelodeon sitcom "True Jackson, VP." 

But it wasn't until 2014 that Palmer appeared in a Season 10 episode of "Grey's Anatomy as a young pregnant patient named Sheryll who comes to Grey Sloan to get into Cristina Yang's HLHS trial. Though she goes into labor before being accepted into the program, her determination and strength has her advocating for herself even through her contractions. But Yang is a brick wall, refusing to budge. The birth of Sheryll's baby is a heart-wrenching scene in which Palmer's character breaks emotionally. Ultimately, Sheryll is rejected from the trial, even as she holds her newborn baby.

Palmer's gone on to act in hit movies like "Hustlers" and "Nope," plus shows like "Scream Queens," "Turnt Up with the Taylors," and "Scream: Resurrection." "Turnt Up" won Palmer an Emmy for Outstanding Actress in a Short Form Comedy or Drama Series. This Facebook Watch parody series features various characters played by Keke Palmer and gave the actor a chance to be a producer. Of the unique opportunity of takin on multiple characters, Palmer told Harper's Bazaar, "I just thought, 'Why not? It could be fun. I've never done it before.'"

Millie Bobby Brown

As well-known as "Stranger Things" actor Millie Bobby Brown is, it's hard to believe that she was just an infant when "Grey's Anatomy" first aired. In fact, her acting career hasn't even reached the ten-year mark as of this writing. The English actor's first credit was in 2013 with two episodes on the fantasy drama "Once Upon a Time in Wonderland." She followed that up with a starring role in the short-lived series "Intruders."

In "Grey's" Season 11 episode "I Feel the Earth Move," Brown played a young girl, Ruby, who calls into Grey Sloan after an intense earthquake shakes Seattle. Almost her whole performance is her voice only as Dr. Owen Hunt, played by Kevin McKidd, speaks to her over the phone and talks her through helping her mother who may have been injured in the quake as she was unconscious. In the end, she revives her mother and at the hospital we finally get to see her in person — a tearful reunion between Owen and Ruby ensues at the helipad and Owen praises the young girl for her heroic efforts.

Funny enough, Brown didn't know the ins and outs of the "Grey's" universe when she appeared on the series. As she told Maddie Ziegler for Interview, "I don't actually watch 'Grey's Anatomy.' When I was in it, I kind of knew that it was a big deal." 

Leslie Odom Jr.

Star of stage and screen Leslie Odom Jr. first made a name for himself in the musical "Hamilton," in which he portrayed Aaron Burr. Odom's first on-screen credit was in Kevin Hart's 2004 show "The Big House." Two years later, he appeared in "CSI: Miami," "Vanished," and "Big Day." Of his early television career, he once said in Interview, "I love TV—the little bit of money that I made in TV allowed me to work Off-Broadway for six months and not be completely destitute."

In "Grey's Anatomy" Season 5 episode "There's no 'I' in Team," Odom's character P.J. is part of a storyline where Bailey has organized a huge "kidney exchange" between a dozen different people. P.J. is donating a kidney to someone because someone else is donating a kidney to his father. But, it turns out, P.J. is actually doing it for the $10k his dad is giving him, which puts the whole "domino surgery" at risk. Ultimately it takes his dad having a seizure and a berating from Karev before P.J. comes around and tearfully goes to his father's bedside.

While Odom's emotional performance was memorable, Ellen Pompeo also had a noteworthy episode. One, she showed us a rare "Mere" screwup when she drops the kidney on the floor during one of the surgeries. Thankfully, Bailey calls "five-second rule!" and Meredith quickly scoops it up. Second, even with her slippery fingers, Meredith took home the coveted kidney in a jar, leaving Cristina jealous and slack-jawed.

Christina Ricci

Though it was more than three decades ago, many will always see Christina Ricci as Wednesday Addams from "The Addams Family." Leaving such a lasting effect after only her second year in the entertainment business is quite an accomplishment. From there, the actor basically grow up in front of audiences, appearing in movie after movie — "Now and Then," "That Darn Cat," and "Sleepy Hollow" to name a few — as well as shows like "Malcolm in the Middle," "Ally McBeal," and "Grey's Anatomy."

In 2006, Ricci appeared in two episodes as Hannah Davies. A rookie paramedic, Hannah ends up getting herself into a very dangerous situation with a patient who was shot with a bazooka. When the doors open to the ambulance, Davies's hand is inside the patient's chest, trying to stop the bleeding. When they discover there's possibly live ammunition still inside his chest, Hannah must keep it there until the bomb squad arrives. Unfortunately, at some point, she panics, rips her hand out and runs, leaving Meredith to shove her hand into the patient — and with the bomb. This would be a two-parter and Hannah would show her regret and shame for letting fear take over, but she was still lauded as a hero.

For her performance on "Grey's," Ricci was nominated for an Emmy for Outstanding Guest Actress in a Drama Series, her first nomination. She would go on to be nominated for her work again in 2022, for the series "Yellowjackets."

Neve Campbell

Neve Campbell first became a household name while playing Julia Salinger in "Party of Five" from 1994 to 2000. The actor kept busy while she was on the show, appearing in some high-profile films like "The Craft," the "Scream" franchise, and the infamous "Wild Things," in which her kissing scene with Denise Richards caused quite a stir. After "Party of Five," Campbell continued doing movies and snagged spots on TV shows like "Medium," starring Patricia Arquette and had a recurring role in "The Philanthropist."

In Season 5 of "Grey's Anatomy," Campbell appears in two episodes as one of Derek Shepherd's four sisters. Meredith had called her to see if she would donate a nerve to Derek to help heal the hand that was injured in the plane crash. Derek is reluctant to let his sister do this and after some sibling banter between the two, it's clear their relationship has been rocky over the years. Thankfully, the surgery was a success and Meredith and Liz had a sweet "sisterly" moment when Meredith shared the news of her pregnancy with Liz when no one else knew.

"Scream" fans might've thought it was sort of weird to see Campbell play one of Derek's siblings in "Grey's." As she told E! News ahead of the ep's premiere, "It's just funny because we played pseudo love interests [in 'Scream 3'] now we are brother and sister!"

Taye Diggs

If there's one man in Hollywood who has seemed to have done it all, it would be Taye Diggs. Over the course of his career, he's appeared in both primetime and daytime televisions series, including "Guiding Light," "Ally McBeal," and "Will & Grace." He's also landed roles in films such as "The Best Man," "Cake," and "How Stella Got Her Groove Back." Diggs has even competed on "The Masked Singer" as The Serpent, making it to the final four.

In Season 3 of "Grey's Anatomy," Diggs was brought on to play Dr. Sam Bennett, a friend of Addison Shepherd. Addison has gone to visit the office that she would ultimately work at alongside Sam in the spin-off series "Private Practice." During this two-parter we get to see Sam — and other "Private Practice" characters — treat patients in the office and introduce viewers to their lives and their own dramatic storylines.

When Diggs appeared on "The Ellen DeGeneres Show" to discuss the "Grey's" offshoot, she asked if "Private Practice" was going to feature character nicknames, too. "I think they're trying to steer away from all of those nicknames to try and give us our own style, but I always thought if they did go in that direction, I could be McChocolatey," he quipped, before assuring DeGeneres he was only kidding.

Eric Stoltz

Eric Stoltz got into the entertainment business in the '70s, with his most notable role being that of Rocky Dennis, a boy with a massive facial skull deformity, in the movie "Mask," starring Cher. Of course many will remember him as the drug dealer who helps revive Uma Thurman's character in "Pulp Fiction." He was also a series regular on several television shows, including "Mad About You," "Chicago Hope," and "Madam Secretary."

In Season 5 of "Grey's Anatomy," Stoltz played death-row inmate William Dunn over the span of three episodes. In one of the more disturbing scenes, Cristina Yang asks what he did and he matter-of-factly tells her how he slit a woman's throat. "I thought it would be terrifying or sad or something, but it wasn't. It was just... kind of fun," he said. Days away from execution, Dunn needs emergency surgery. However, Dunn would rather skip the surgery and die in the hospital; Meredith Grey wants his organ for a dying child. In the end, they saved Dunn so he could die by execution, which as strange as it seems, Meredith attended.

Before he appeared on "Grey's," Stoltz directed two episodes of the primetime drama. Of what it was like wearing another hat on the set, he told E! News, "The cast had some fun at my expense when they realized I was no longer directing and I was merely acting, handcuffed to a bed."

Ernie Hudson

"Ghostbusters" star Ernie Hudson has been gracing the small and big screen for over forty years and has appeared in some of the biggest hits. For the TV, that would be classic shows like "Fantasy Island" and "Diff'rent Strokes," as well as more recent series like "ER" and "Desperate Housewives." Hudson's film credits include "Redemption," "The Crow," and "Ghostbusters: Afterlife."

In "Grey's Anatomy" Season 8 episode "Put Me in, Coach," Hudson played the chief of surgery for an opposing hospital Seattle Grace is playing softball against. Chief McDougall and Owen Hunt, who is acting chief at the time, go at it as coaches, talking smack during practice. During the actual game, Hudson even gets an at bat and hits a home run, complete with victory dance. Unfortunately for SG, Lexi Grey shows unsportsmanlike conduct, throwing a ball at an opposing player, and the whole thing erupts into yelling.

Interestingly, Hudson was actually being considered for the role of Chief Richard Webber, played by James Pickens Jr. Hudson told MadameNoire that "Grey's" show creator Shonda Rhimes liked his work and had asked him to come in and read for the part. "I'm not readin', I'm sorry," Hudson said at the time, now regretting that decision. "Now, of course, it's in its tenth season and he's making a zillion dollars an episode," he quipped.

Mandy Moore

You might know Mandy Moore from playing mom Rebecca Pearson on "This is Us," but almost twenty years before that show started, Moore was in the recording studio, working on her first hit pop song, "Candy." In the early 2000s, she would continue pursuing music as well as acting, appearing in hit films like "A Walk to Remember" and "Princess Diaries."

In 2010, Moore appeared on "Grey's Anatomy." At the end of Season 6, an active shooter attacked Seattle Grace, and Moore played a patient named Mary who pretends to be dead to save herself. She also helps Dr. Bailey tend to someone who had been shot. In Season 7, Moore's character returns to the hospital for the surgery she was supposed to undergo on the day of the shooting. The whole episode was in a documentary style, with side interviews for the characters. Sadly, Mary never wakes up from her surgery. Losing Mary is incredibly hard for Bailey since they had been there for each other during that tragic day, and was likely tough on the viewers as well. It was ranked by Cosmopolitan magazines as one of the most heartbreaking losses of the series in 2020.

When Moore was invited to head back to "Grey's," she leapt at the chance, though she did not know what fate had in store for Mary. As she told MTV News, "I'm not sure what they have planned necessarily, but hopefully there will be a little less blood involved than in the finale."