Over 21 seasons, dozens of actors-turned-doctors have walked the halls of Grey Sloan Memorial Hospital — some leaving a more lasting impact than others. While many fans still hope for their return, the often controversial exits of these actors make comebacks far from simple
Twenty-one seasons and 440 episodes later, Grey’s Anatomy remains one of the longest-running series on television, captivating viewers for two decades. It has become a cultural phenomenon, transcending generations and, thanks to streaming, attracting a new generation of fans who weren’t even born in 2005, when the first episode aired.
March 27 marks the 20th anniversary since Seattle Grace — now Grey Sloan Memorial Hospital — first opened its doors on ABC. The world created by Shonda Rhimes bears little resemblance to its humble beginnings: while the core of the plot still revolves around a healthcare facility, the show has evolved to reflect modern times, introducing new characters after the departures of the original cast.
Dozens of actors-turned-doctors have captivated audiences; others, however, slipped away quietly, their characters fading from the story as soon as they lost relevance. Fans of Grey’s Anatomy quickly learned not to get too attached, knowing that at any moment, an unexpected event could change everything: fires, attacks, plane crashes… Over 21 seasons, the show has seen it all, often leaving viewers in tears. But what has become of the main characters who first graced the halls of Grey Sloan Memorial?
Ellen Pompeo as Meredith Grey
Pompeo’s acting career is most notably defined by her role as Meredith Grey. Although the 55-year-old actress has been involved in many other projects, she will always be remembered — whether she likes it or not — for playing the iconic doctor protagonist of Grey’s Anatomy. She accepted the role that would change her life at 35, and two decades later, she remains deeply connected to it.
Though no longer a regular cast member, having chosen to leave the series, she occasionally returns. She also serves as a producer on the show, giving her the power to decide when to come back and influence the storyline. Her on-again, off-again relationship with Derek Shepherd (played by Patrick Dempsey), at times bordering on toxicity, was one of the central plotlines during the early seasons. However, the real dynamic between the two protagonists wasn’t always as it appeared on screen
In 2018, Pompeo revealed in an interview with The Hollywood Reporter that for years, she was earning less than Dempsey, and that the show’s producers had used Dempsey as leverage to deny her a pay raise. Everything changed in 2015 when Dempsey left the production.
“For me, Patrick leaving was a defining moment,” she said. “They could always use him as leverage against me — ‘We don’t need you; we have Patrick’ — which they did for years. I don’t know if they also did that to him, because he and I never discussed our deals. There were many times where I reached out about joining together to negotiate, but he was never interested in that.”
After reaching a new deal, Pompeo earned more than $20 million a year. As she later explained in a 2020 podcast, she “made a decision to make money, and not chase creative acting roles.”
Now that the actress has left her role as Meredith Grey behind, she has embarked on other projects. On March 19, her eight-part miniseries American Family premiered, where she portrays Kristine Barnett, a mother who adopts a daughter with dwarfism, and whose case eventually ends up in court. This marks the first of several projects through which she aims to distance herself from the character she’s been playing for years — and continues to return to.
Patrick Dempsey as Derek Shepherd
Despite being one of the leads, Dempsey, 59, decided to leave the production due to disagreements with the series’ creator. The tragic end of his character, the neurosurgeon, shocked an entire generation who never expected him to say goodbye to Grey’s Anatomy. The actor later revealed that his decision was driven by the long work hours and the negative atmosphere on set.
Years after his departure, the series’ executive producer claimed that he “was terrorizing the set”: “Some cast members had all sorts of PTSD with him. He had this hold on the set where he knew he could stop production and scare people.”
However, other colleagues who supported Dempsey said that he was very attentive to them. His departure left a wound that seemed incurable to many fans, but Dempsey showed he was capable of adapting to new opportunities. After leaving the series, he has starred in eight other projects, with Ferrari (2023) being one of the latest and most successful in his career.
Patrick Dempsey a was completely shocked, and then I started laughing, like, this is a joke, right?” he said.
His personal life has also attracted its fair share of celebrity gossip. He is married to makeup artist and cosmetics founder Jillian Fink, with whom he shares three children. In 2015, after 16 years of marriage, he filed for divorce. However, a year later, they reconciled, and he has since become the best ambassador for his wife’s brand.
Katherine Heigl as Izzie Stevens
The role of Izzie Stevens catapulted Heigl, 46, to international fame, making her one of the most beloved characters on the show. With her acting talent and emotional depth in both romantic and dramatic scenes, she became one of the most sought-after actresses of the 2000s. While filming Grey’s Anatomy, she also starred in other successful projects, such as 27 Dresses and Knocked Up.
In 2007, she won an Emmy Award for her role in Grey’s Anatomy, surpassing other castmates, and was considered one of the highest-paid women in film, earning over $10 million. However, just as quickly as fame arrived, it faded. Heigl was one of the first to leave Shonda Rhimes’ series, choosing to step away to focus on her family.
Another factor that influenced her decision to leave was the diminishing relevance of Iggie, who was given less interesting storylines. While Heigl chose to leave the show, she later gained a reputation as a “complicated” actress to work with.
“I was just vibrating at way too high of a level of anxiety. For me, it’s all a bit of a blur, and it took me years to learn how to deal with that, to master it. I can’t even say that I’ve mastered it,” she admitted in 2023 to Variety. Despite having plenty of job offers, her career trajectory was never the same. Her most recent project was the 2023 series Firefly Lane.
Sandra Oh as Cristina Yang
Cristina Yang, a character as hated as she was beloved for her sharp personality, earned Sandra Oh, 53, a Golden Globe in 2006 and made the iconic phrase “you’re my person” a motto for an entire generation. Unlike some of her castmates, her departure was relatively peaceful — she simply wanted to explore new acting opportunities.
Since leaving the show in 2014, many fans have hoped for her return. When asked by ET Canada if she would consider reprising her role on Grey’s Anatomy, she replied: “I’m extremely grateful that you’re asking me that question because that means that people are still invested and interested in Cristina Yang.”
She is one of the few lead actresses from Grey’s Anatomy who has successfully continued her career without being defined by a single role. She has worked across film, theater, and television, most notably starring in the acclaimed series Killing Eve, which earned her another Golden Globe in 2019.
Justin Chambers as Alex Karev
The character of Alex Karev underwent the most significant evolution throughout the series. Initially disliked — both on and off the set — Chambers, 54, eventually became one of the show’s most beloved figures. He was also one of the few original cast members to stay until season 16, when he suddenly disappeared without explanation. His fans were disappointed he didn’t get a proper farewell.
The official reason given for Chambers’ departure was a desire to explore other projects, but in reality, he has had only two minor roles since leaving in 2020. The most persistent, albeit unofficial, explanation is that tensions with showrunner Shonda Rhimes led to his abrupt exit. Despite his forced departure, Chambers participated in the Grey’s Anatomy reunion at the 2024 Emmy Awards.
T. R. Knight, as George O’Malley
Knight, 51, was the first main cast member to leave Grey’s Anatomy, exiting in the fifth season. While his departure wasn’t entirely controversial, his character’s ending was one of the cruelest and most tragic in the award-winning series. Like his co-star Katherine Heigl, he expressed frustration over dwindling screen time and also endured personal attacks on set.
He was targeted by co-star Isaiah Washington, who was ultimately fired for making homophobic remarks, and openly spoke about the discrimination he faced during filming. Despite the challenges, he later made a brief return in a later episode and has maintained a good relationship with some of his former castmates, including Ellen Pompeo.
Since leaving Grey’s Anatomy, he has remained active in the entertainment industry, though with limited
success, focusing primarily on theater and Broadway musicals.
James Pickens Jr. as Richard Webber and Chandra Wilson as Miranda Bailey
The only two original cast members still on Grey’s Anatomy are James Pickens Jr. and Chandra Wilson, who portray the most seasoned doctors at Grey Sloan Memorial Hospital. For Pickens Jr., landing the role of Dr. Webber at 50 was a career-defining opportunity that changed his life.
While both actors have taken on other projects over the years, most have been minor roles or directly connected to the Grey’s Anatomy universe.
Chyler Leigh as Lexie Grey
Leigh, 42, first appeared in the third season but quickly became one of the most beloved characters. As Meredith Grey’s half-sister — who initially kept her at a distance due to their complicated family ties — Lexie played a crucial role in the series until her tragic and unexpected death. Though her departure wasn’t originally planned, the actress’s decision to leave led to a script change, placing her among those who perished in the plane crash that claimed the lives of several main characters.
Years later, she made a brief return in special episodes where deceased characters reunite with Meredith Grey, who is in a coma due to the coronavirus. Since leaving Grey’s Anatomy, she has taken on various roles, with the TV series Supergirl being her most successful project to date.
Eric Dane as Mark Sloan
The character of Mark Sloan was inextricably linked to Lexie Grey, and her departure inevitably led to his. Although Eric Dane, 52, initially stated that he left Grey’s Anatomy to pursue other projects — a common explanation for many cast exits — he later revealed that the decision wasn’t entirely his own. “I didn’t leave so much as I think I was let go” he admitted.
During his time on the show, Dane struggled with drug and alcohol issues, even seeking treatment at a rehab facility. While he insists this wasn’t the direct cause of his dismissal, he acknowledges that it “didn’t help.” He also cited budget constraints as a factor, believing the series could continue without him. Despite his exit, he was among the actors invited back for the reunion episode that thrilled longtime fans.
Since leaving Grey’s Anatomy, Dane has taken on various roles with mixed success, but his most notable recent project is Euphoria.
Camilla Luddington as Jo Wilson
She was one of the last to join Grey’s Anatomy as a new intern, but over time, she has become one of the show’s standout stars, especially after many of her original castmates departed. Jo Wilson’s character had a long-running relationship with Alex Karev, eventually marrying him. However, after the actor’s abrupt exit from the series, Jo’s storyline evolved, introducing new relationships and personal growth.
With the show operating on a reduced budget, her character no longer appears in every episode, but she remains committed to “continuing this adventure” until the time comes to move on. Despite receiving other offers, the actress has focused her career almost entirely on Grey’s Anatomy, turning down other offers that have come her way.
Sara Ramírez as Callie Torres and Jessica Capshaw as Arizona Robbins
The fictional couple of Callie Torres and Arizona Robbins became one of the most beloved in Grey’s Anatomy, but nothing lasts forever, even less so on Grey’s Anatomy. After a decade playing Torres, Sara Ramírez left the series on a high note, with her character starting a new life in New York. At the time, Ramírez stated they wanted to focus on their personal life.
Later, Ramírez publicly came out as non-binary and shared that for years, they feared their sexual orientation might negatively impact their career. Since leaving Grey’s Anatomy, they have taken on new roles, most notably portraying Che Diaz in And Just Like That…, the Sex and the City sequel on MAX.
A few seasons later, Jessica Capshaw also left Grey’s Anatomy, though not by choice. According to reports, the writers decided that her character, Arizona Robbins, was no longer of interest.
“For the past 10 years, I have had the rare privilege of not only playing Arizona Robbins but also being madly in love with playing her,” Capshaw wrote on X (formerly Twitter). “I am sad to see her go, but I am consoled by the idea that she will continue to live on and on in all of our consciences.”
Despite her departure, she later made a brief return to reprise her role as the beloved surgeon.
