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."

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. 

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.

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.'"

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.

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!"

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."

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."