Grey's Anatomy (2005– )
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Kate Walsh (Addison Montgomery) will be starring in a spin-off, "Private Practice", but will still do guest appearances and did several cross-overs between the two shows until Private Practice was cancelled in 2013
Isaiah Washington (Preston Burke) was fired from the show, therefore will not be returning after Season 3. But made a guest appearance in season 10.
Brooke Smith (Erica Hahn) has chosen not to renew her contract, because she felt the writers weren't really doing anything with her character.
T.R. Knight (George O'Malley) asked to be released from his contract at the end of Season 5 so he can pursue other projects.
As of the beginning of Season 6, Katherine Heigl (Izzie Stevens) has stepped back as a regular and is now recurring, due to pursuing other projects and adopting a daughter. She made her last appearance in mid-season 6.
Both Nora Zehetner (Reed Adamson) and Robert Baker (Charles Percy) did not return for Season 7, as both their characters were shot dead in the Season 6 finale.
Lexie Grey (Chyler Leigh) left the show to spend more time with her family and her character died Season 8, episode 24.
Mark Sloan (Eric Dane) made his last appearance season 9, episode 2.
Kim Raver (Dr. Teddy Altman) left in the season 8 finale, however returns during Season 14 as a recurring character and becomes a series regular in season 15.
Dr. Heather Brooks (Tina Majorino) was killed off in season 10, episode 2.
Sandra Oh (Dr. Cristina Yang) left the series as a main character in the season 10 finale after deciding to spend more time persuing other career avenues. Along with her went Gaius Charles (Dr. Shane Ross). Tessa Ferrer (Dr. Leah Murphy) left the show on that same episode as well. Her character was fired from the hospital.
Patrick Dempsey (Dr. Derek Shepherd) left the show towards the end of season 11. His character was killed off. Edit