Quick Answer: Having been in existence for twelve years and counting, Grey's Anatomy's large ensemble cast has morphed considerably over the show's duration. In addition to the large number of actors who leave, their departures have been very publicized. The decision of who should remain and who should go may at times seem random, but more often than not the actors' departures are determined by the actors' contracts, actors deciding to pursue other opportunities, writers following plot lines, and personal issues between the cast and crew.
Grey's Anatomy (2005 - ) is a long-running medical drama about a teaching hospital with a large cast. As a result, quite a few characters die on the show or leave to pursue other interests or join other medical facilities. In addition to the large number of actors who leave, their departures have been very publicized. The decision of who should remain and who should go may at times seem random, but more often than not the actors' departures are determined by the actors' contracts, actors deciding to pursue other opportunities, writers following plot lines, and personal issues between the cast and crew. Here's a round-up of every character who has left Seattle Grace and why.
Denny Duquette (Jeffrey Dean Morgan) is a heart patient at the hospital with whom Dr. Izzie Stevens (Katherine Heigl) falls in love. In an attempt to save his life she cuts his LVAD wires so that he is moved up the transplant list. Unfortunately, the transplant surgery results in a stroke, and he dies, leaving Izzie $8.7 million dollars in his will (S2:E27). She uses the money to open a clinic in his name, and he continues to periodically appear as a memory and/or ghost on the show through Season 5 (S5:E23).
Jeffrey Dean Morgan and Katherine Heigl on Grey's Anatomy
The following season, one of the departures was less amicable. In October 2006, Isaiah Washington (who plays Dr. Preston Burke) had an off-screen confrontation with Patrick Dempsey (who plays Dr. Derek Shepherd) during which Washington used a homophobic slur directed towards fellow actor T.R. Knight, who plays George O’Malley. Washington's character was abruptly written off the show when Washington was fired for the incident. The writers worked around the conflict, having Burke leave Dr. Cristina Yang at the altar (S3:E25). He isn't seen again until Yang herself is written off the show 7 seasons later (S10:E22).
Also that season, Dr. Ellis Grey (Kate Burton), Meredith Grey's (Ellen Pompeo) mother and Dr. Richard Webber's (James Pickens, Jr.) former lover, dies of early onset Alzheimer's (S3:E17). Ellis appears on the show from time to time in the memories of her daughter and Webber and sometimes via flashbacks to when she was a young intern herself (played by Sarah Paulson and Sally Pressman).
Kate Burton and James Pickens, Jr.
Sometimes an actor's leaving not only suits the plot but also leads to greater opportunities for him or her. Shonda Rhimes approached Kate Walsh, who plays Dr. Addison Montgomery, about leaving Grey's Anatomy at the end of Season 3 (S3:E25) and being the lead on a spin-off show called Private Practice (2007 - 2013). Writing Addison off the show was easy; she was Dr. Shepherd's ex-wife and Dr. Sloan's ex-girlfriend. Seeing them both move on with their lives makes her want to move on with hers. She leaves Seattle Grace Hospital to work at Oceanside Wellness Center in Santa Monica. Addison is occasionally called back to Seattle Grace (later called Grey Sloan Memorial) for emergencies.
Kate Walsh as Dr. Addison Montgomery in Grey's Anatomy
Season 3 also had its fair share of familial deaths. George's father Harold O'Malley (George Dzundza) dies after surgery to remove his extensive tumors (S3:E12). Meredith's stepmother Susan Grey (Mare Winningham) dies at the hands of Meredith and her fellow doctors from complications arising from hiccups (S3:E23).
In a considerably less dramatic plot line than the show is known for, Dr. Sydney Heron (Kali Rocha) is last seen breaking up with Derek after one date (S4:E8).
The next departure makes up for it. Rebecca Pope (Elizabeth Reaser) is a pregnant amnesiac patient who falls in love with Dr. Alex Karev (Justin Chambers) after he rescues her from a ferry crash and helps her recover from her facial reconstruction surgery. She eventually goes home with her husband, only to return to Karev, attempt suicide and be admitted to the psychiatric ward (S4:E17).
Due to the publicity of the incident between Dempsey and Washington in 2006, Knight announced to the press that he was homosexual. While Knight remained on the show for a few more seasons, he ultimately quit due to decreased screen time and what he called a "breakdown in communication" with show creator Shonda Rhimes. George is given a hero's death; on his way home to tell his mom he's joined the army, he is killed while pushing a stranger out of the way of a moving bus (S5:E24).
According to actress Brooke Smith, her character, Dr. Erica Hahn, was likely dropped from the show at the request of the network. Hahn walks off screen after a fight with her lover Dr. Callie Torres (Sara Ramirez), never to be seen again (S5:E7). Rhimes released a statement saying the character was dropped because there was no chemistry between the two women.
Also in Season 5, Nurse Rose (Lauren Stamile) transfers to pediatrics after Derek Shepherd leaves her for Meredith (S5:E2). Intern Sadie Harris (Melissa George) quits the program after her self-harming tendencies get her in trouble with Dr. Webber (S5:E15).
Katherine Heigl's departure was one of the most publicized of the series. She has said she left the show during Season 6 to spend more time with her family. However, it is well known that Heigl was upset by her low screen time in Season 4, which led her to reject an Emmy nomination, citing a lack of “material…to warrant an Emmy nomination." This rejection upset the show’s producers. Stevens has terminal cancer in Season 5, only to recover, make a mistake with a patient and be fired. She returns briefly to see her estranged husband before never being seen again (S6:E12).
Grey's lost a handful of other actors that season in addition to Heigl. Nurse Olivia Harper (Sarah Utterback) is let go by Dr. Derek Shepherd during the merger with Mercy West Hospital (S6:E3). Dr. Reed Adamson (Nora Zehetner) and Dr. Charles Percy (Robert Baker) die of gunshot wounds sustained in the mass shooting at the hospital (S6:E23 and S6:E24, respectively).
Nora Zehetner and Robert Baker
Steven W. Bailey played Joe, the bartender at the Emerald City Bar through 2010, after which his character is never seen again. Joe is one of the lucky few who just seems to disappear, rather than have tragedy befall him (S7:E9). Interestingly, Steven W. Bailey also made three appearances on the show as Jeremy the anesthesiologist in 2005.
Steven W. Bailey as Joe the bartender
Steven W. Bailey as Jeremy the anesthesiologist
For the remainder of Season 7, we see the loss of several minor characters. Dr. Robert Stark (Peter MacNicol) is the interim Chief of Pediatric Surgery for a year when Dr. Arizona Robbins takes a year off to work in Malawi (S7:E20); Dr. Lucy Fields (Rachael Taylor) is an obstetrician who leaves Seattle to treat children in Africa after Karev dumps her (S7:E22); and Meredith’s father, Thatcher Grey (Jeff Perry), is last seen after being diagnosed with a kidney stone (S7:E14).
Kim Raver, who played Dr. Teddy Altman, left the show on her own when her contract ended after Season 8. Altman, who had been in the Army with Dr. Owen Hunt, is offered a position by the U.S. Army Medical Command but doesn't want to leave Hunt, who fires her so that she will go (S8:E24).
Season 8 also sees the deaths of two of the show's major characters. The star-crossed lovers Dr. Lexi Grey (Chyler Leigh) and Dr. Mark Sloan (Eric Dane) were both killed due to injuries sustained in the plane crash during the Season 8 finale (S8:E24 and S9:E2, respectively). Dane may have been cut due to the network’s desire to reduce the show's budget, but officially the split was mutually decided on and allowed him to pursue other projects such as The Last Ship (2014 - ), while Leigh's departure was due to a desire to spend more time with her family.
Eric Dane and Chyler Leigh
Like Webber's former lover Ellis Grey, his wife Adele (Loretta Devine) suffers from early onset Alzheimers. She dies of a heart attack in Season 9 (S9:E10).
Sandra Oh, who plays Dr. Cristina Yang, left the show at the end of Season 10 despite having two more seasons in her contract. Yang leaves Grey Sloan Memorial when Dr. Burke offers her the position of Director of Cardiothoracic Surgery at the Klausman Institute for Medical Research in Zurich, taking intern Shane Ross (Gaius Charles) with her (S10:E22).
Ellen Pompeo and Sandra Oh
As we've seen, it wouldn't be Grey's Anatomy if we only lost one actor in a season. In addition to losing Dr. Yang, intern Heather Brooks (Tina Majorino) dies after being electrocuted during a storm (S10:E1), and intern Leah Murphy (Tessa Ferrer) is let go by Chief Webber (S10:E24).
Dr. Nicole Herman (Geena Davis) has terminal cancer in Season 11. She spends her remaining time teaching Dr. Arizona Robbins to be her replacement. Robbins eventually convinces her to allow Dr. Amelia Shepherd (Dr. Derek Shepherd's sister) to try to surgically remove the tumor, and while the operation saves her life, it leaves her blind. Unable to operate, Herman leaves the hospital to go to the Blind Institute to learn how to live her life (S11:E14).
But of all the departures from the show, that of Patrick Dempsey's character Dr. Derek Shepherd was the most controversial. Unlike many other television shows, the story of Grey's Anatomy was not a will-they-won't-they (after all, Meredith and Derek had already hooked up in the events leading up to the pilot). Instead, the show asks a different question: would the deeply damaged and "dark and twisty" Meredith be able to keep the seemingly perfect McDreamy?
Patrick Dempsey and Ellen Pompeo
The question is finally answered in "How To Save a Life" (S11:E21). Meredith and Derek decide they don't want a divorce; they want to work on their marriage. But Shondaland is a cruel place. Soon after the couple reconciles, Derek's car is hit by a truck. He is brought to Dillard Medical Center, where a doctor tells the arriving ambulance crew "we are not a trauma center." Due to the hospital's incompetence and the extent of his injuries, Derek dies in the hospital.
According to Dempsey, the plot came about naturally. Rhimes has said that because of certain plot lines in the season, Derek either had to die or the marriage had to fail. Not wanting to break up the two characters, they decided to have him die instead. Whether killing off McDreamy was a good plan is debatable, but the fans certainly didn't think so and signed a petition to prove it.
The fans had good reason to hope that Derek would somehow return. After all, not only had Derek survived a gunshot (S6:E23) and a plane crash (S8:E24), but Meredith has had her own share of near-death experiences as well. Meredith survives an exploding bomb in the operating room (S2:E16), has a burst appendix (S3:E4), drowns and has no heartbeat for over an hour (S3:E16), is with Derek in the plane crash that kills Lexi and Sloan (S8:E24), and nearly bleeds to death during child-birth (S9:E24), twice (S11:E23).
Jeffrey Dean Morgan, Anna Maria Horsford, Monica Keena and Kyle Chandler
Yet, Meredith lives on, and it appears that despite Dempsey having two more years on his contract, Derek will never return to Grey’s Anatomy.
The numerous deaths and departures on Grey's Anatomy are some of the most publicized, debated, and protested on television. Though a simple plane crash or career change may determine the end of a character's arc on Grey's, it's clear that what has gone on behind the scenes in the past twelve years is far more complicated.