David Duchovny left The X-Files after the seventh season partly due to a contract dispute. He appeared in episodes of the eighth season and just one of the ninth and final. His character, Special Agent Fox Mulder, was abducted at the end of season seven, returned to Earth, experimented on and later went into hiding. The series introduced new FBI agents played by Robert Patrick and Annabeth Gish to help fill the void. Duchovny returned for both revival seasons on Fox.
A recent example, and not the norm, ABC canceled the revived Roseanne after Roseanne Barr's racist tweet. However, the show went on—sort of. After cancellation, ABC announced The Conners, a spinoff of Roseanne, without Barr. She'd have no financial or creative ties to the new show. The Conners killed off the Roseanne Conner by way of opioid overdose.
Steve Carell said goodbye to Dunder Miflin's Scranton branch at the end of season seven when his character, Michael Scott, moved away with his fiancé Holly (Amy Ryan) to help care for her ailing parents. The Office went on for two more seasons and Carell returned in the season nine finale, which was also the series finale. To fill the void, The Office added several characters, including James Spader's Robert California.
The ABC fantasy series lost the majority of its main cast, including Jennifer Morrison, Josh Dallas and Ginnifer Goodwin, ahead of the seventh and final season that served as a reboot of the series. The departed main characters eventually returned to the show ahead of the series finale.
Michael J. Fox starred in the first four seasons of political comedy Spin City, but left after announcing his diagnosis with Parkinson's disease. Ahead of his exit, the show introduced Heather Locklear's Caitlin, and after Fox's exit Charlie Sheen joined the cast as the new deputy mayor. Fox later returned for a handful of episodes during the sixth and final season.
Charlie Sheen's infamous Two and a Half Men public meltdown resulted in him being fired from the hit CBS comedy. In his place, Ashton Kutcher. The character of Charlie Harper was killed off, only in a twist they had him be alive…until the series finale where he was once again killed.
Scrubs did something strange, although not unheard of, for what would be its final season. The ninth and final season featured a new cast and shift from a hospital to a medical school with Donald Faison and John C. McGinley remaining. Zach Braff and Sarah Chalke appeared sporadically
After Nashville was canceled by ABC and revived by CMT, the unthinkable happened: the nighttime country music soap killed of Rayna Jaymes and series star Connie Britton left the show in season five, the show ended with season six. Britton later returned in the series finale as part of a flashback-dream situation and for the musical show's final group number.
Clayne Crawford was fired from Fox's remake of the beloved film franchise following on-set outbursts and spats with costar Damon Wayans. His character, Riggs, was shot in the season two finale and died in the season three premiere. Fox added Seann William Scott to the cast for the third season. Meanwhile, Wayans announced his intent to leave the show after the third season.
Christopher Meloni turned in his badge and gun in between seasons 12 and 13. In the season 12 finale, Meloni's Detective Stabler was involved in a squad room shootout and when season 13 started it was revealed to Benson (Mariska Hargitay) that her longtime partner had retired. The show brought in new detectives played by Kelli Giddish and Danny Pino.
By the time ER ended after 15 seasons the medical drama had a completely different cast than when it started. The first of its lead characters to go was Sherry Stringfield in season three, followed by George Clooney in season five and Julianna Margulies in season six. Top-billed Anthony Edwards, Dr. Greene on the series, left the show in season eight when his character died of a brain tumor. He returned in a flashback episode in the final season. Noah Wyle was elevated to lead character following Edwards' exit, but Wyle ended up leaving after season 11. He appeared in season 12 and recurred in the final season.
Nina Dobrev played a variety of characters on TVD over her six seasons on The CW drama. One of her characters, Elena, had her life linked to another character's, putting her in a coma. She returned in season eight for the show's series finale where Elena got a happy ending with Damon (Ian Somerhalder).