==== T. R. Knight ====
Den 7. maj 2009, rapporterede E! Onlin's Marc Malkin, at Knight ikke ville vende tilbage til sæson 6. Knight var ikke tilfreds med udviklingen af serien, da hans karakter, George, fik mindre tid på skærmen, dette førte til at han bad om at blive frigivet fra hans kontrakt i December 2008. <ref>{{cite news|last=Malkin|first=Marc|title=T.R. Knight: A Grey's Anatomy Goner|publisher=[[E! Online]] |date=27. maj 2009 |url=http://www.eonline.com/uberblog/marc_malkin/b125996_tr_knight_greys_anatomy_goner.html| access-date =28. maj 2009}}</ref> Der havde været fan-spekulationer om at en anden skuespiller ville tage rollen, da George-karakteren ville have massive ansigts forandringer på grund af det der skete i sæson fem finalen, <ref>{{cite news| last = Ausiello| first = Michael| author-link = Michael Ausiello| title = Ask Ausiello: Spoilers on 'Gossip Girl,' 'Dollhouse,' 'Scrubs,' 'NCIS,' 'Grey's,' and more!<!--| work = The Ausiello Files-->| work = [[Entertainment Weekly]]| publisher = [[Time Inc.]]| date = 20. maj 2009| url = http://ausiellofiles.ew.com/2009/05/ask-ausiello--2.html| access-date = 29. maj 2009| archive-date = 26. maj 2009| archive-url = https://web.archive.org/web/20090526203823/http://ausiellofiles.ew.com/2009/05/ask-ausiello--2.html| url-status = dead}}</ref> men New York Daily News's skribenten Patty Lee erklærede at "Hans karakter, Dr. George O'Malley, er død". <ref>{{cite news| last = Lee| first = Patty| title = Source: T.R. Knight's 'Dr. George O'Malley' character officially off 'Grey's Anatomy'| work = [[New York Daily News]]| date = 28. maj 2009| url = http://www.nydailynews.com/entertainment/tv/2009/05/28/2009-05-28_source_tr_knights_dr_george_omalley_character_officially_off_greys_anatomy.html| access-date = 28. maj 2009| archive-date = 27. juli 2009| archive-url = https://web.archive.org/web/20090727080027/http://www.nydailynews.com/entertainment/tv/2009/05/28/2009-05-28_source_tr_knights_dr_george_omalley_character_officially_off_greys_anatomy.html| url-status = dead}}</ref> Rhimes sagde at manglen på George i femte sæson var meningen, for at udvide publikums chok, ved den dramatiske slutning, og sagde at Knight var en "utrolig talentfuld skuespiller" <ref>{{cite news| last = Ausiello| first = Michael| author-link = Michael Ausiello| title = Exclusive: 'Grey's' boss on finale's Izzie-George shocker, Mer-Der 'wedding,' and more!<!--| work = The Ausiello Files-->| work = [[Entertainment Weekly]]| publisher = [[Time Inc.]]| date = 15. maj 2009| url = http://ausiellofiles.ew.com/2009/05/exclusive-greys.html| access-date = 28. maj 2009| archive-date = 27. juni 2009| archive-url = https://web.archive.org/web/20090627025937/http://ausiellofiles.ew.com/2009/05/exclusive-greys.html| url-status = dead}}</ref> Den 17. juni 2009 blev det bekræftet officielt at Knight var fritaget fra sin kontrakt. <ref>{{cite news | url= http://crushable.com/entertainment/tr-knight-officially-departs-from-greys-anatomy/ | title= T.R. Knight Officially Departs From Grey's Anatomy | access-date= 25. juni 2010 | archive-date= 23. juni 2010 | archive-url= https://web.archive.org/web/20100623102547/http://crushable.com/entertainment/tr-knight-officially-departs-from-greys-anatomy/ |url-status=dead }}</ref>.
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