But on Monday night's "Late Show with David Letterman," where Katherine confirmed filming has started on Season 6, the upbeat actress told the host she is hoping "Grey's" is in it for the long haul.
"We have another two years, I think, at least in the contract," Katherine said "Hopefully the show goes, you know, [into] 'ER' time, which would be cool."
While Katherine would like to see her show hit double digit seasons like "ER," which bowed out in April after 15 years, she admitted to not being comfortable with working long hours.
"Our first day back was Wednesday [of last week], and I keep saying this because I hope it embarrasses them – [it was] a 17-hour day," she told Dave. "I think it's cruel and mean."
Also uncomfortable was not having one of her best friends – T.R. Knight – on the set, as his character, Dr. George O'Malley, is not returning for Season 6.
"It was a little weird because [T.R. is] not there anymore," she said.
But things weren't all bad.
"It was actually kind of… great to be back," she said. "All my friends are there and at this point, they're sort of like family."
Katherine, however, refrained from clarifying whether her character comes back from flat lining or, like her on-screen husband Denny Duquette, comes back as a ghost or figment of someone's imagination.
"You last saw Izzie, you know, flat-lining," she said. "I won't give it away but… I'm there so I'm either there as a ghost, on the other side or I survived a disease no one survives."
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