"For some, it's about jumping off into something new. It feels like a very fresh start for everybody," Rhimes said. The ABC show's two-hour season debut is 9 p.m. EDT Thursday.
An on-air promotion has provided a clue about one potential challenge facing Meredith Grey (Ellen Pompeo) and Derek "McDreamy" Shepherd (Patrick Dempsey). It includes a brief scene in which Derek is confronted by nurse Rose (Lauren Stamile).
"I wish there were a good way to say this: I'm carrying your child," Rose tells Derek, whose stunned look might match that worn by "Grey's" fans.
When last seen, McDreamy was embracing Meredith amid a sea of candles after therapy allowed her to see the light about their relationship. Rose's revelation - if it's to be taken at face value - strikes an ominous note for the couple known in shorthand as Mer-Der.
Adding to the mystery: In an ABC podcast in May, Rhimes said Rose isn't pregnant, and was later quoted as saying she wouldn't deceive "Grey's" loyalists. If that's the case, Rose - or the network's promotional department - is quite the manipulator.
Rhimes, who's highly protective of plot twists, won't tip her hand about how the story plays out. But she's openly upbeat about season five.
"We've settled in from all the attention paid and all the hoopla. We feel like we're back to where we were in seasons one and two, in the sense that the writers feel a little bit fearless," Rhimes said. "We know our characters so well at this point that now is the time to take chances."
The Hollywood writers strike that shut down most TV production for months had an unexpected benefit, Rhimes said.
"It was the first time in four-and-a-half years I wasn't working nonstop. It was a chance to sleep and clear my brain. ... I know what happens next for these characters in a way I hadn't known before."
For Drs. Grey and Shepherd, that means a bold step toward commitment. But as Rhimes signals, it's unlikely their path together will be smooth.
The new season brings guest stars Bernadette Peters and Kathy Baker and a new medical man at Seattle Grace: Kevin McKidd, playing a military doctor who Rhimes said "makes an impression" on Dr.
Cristina Yang (Sandra Oh).
There's also a familiar face, Katherine Heigl, despite speculation that the series star might want to shrug off her scrubs.
The talk began this summer, after Heigl said she wasn't submitting her name for Emmy consideration this year because the show didn't deliver the material to warrant a nod. She won a 2007 Emmy for the role of Dr. Izzie Stevens.
"Talk? Who?" Rhimes responds tartly when asked about the issue, adding, "We have every intention of seeing Katherine for the entire season."
Asked if the actress has expressed any desire to leave, Rhimes said, "No, she has not."
"Grey's Anatomy" has provided off-screen drama before, most notably stemming from an ugly clash between cast members Isaiah Washington and T.R. Knight. Washington, who used an anti-gay slur, was fired.
"I have to say we've been through a lot," Rhimes said. She attributes it to "the `Dawson's Creek' phenomenon," in which a "bunch of lovely and young actors" must learn to cope with the sudden fame a TV hit brings.
"These are people who went from living their lives to not being able to walk down the street without paparazzi being able to follow them wherever they go," she said.
Rhimes, a newcomer herself as a series TV producer (she now has a second show, the "Grey's" spinoff "Private Practice"), said she feels as if "everybody has grown up together."
"I drive my little golf cart over to the set and everybody is just really happy. ... So it's nice to see that we're growing into it," Rhimes said.
Does that mean no more surprises?
"I would be shocked if there were no more surprises," she said. "It's the nature of the beast. I don't necessarily feel the same about `Private Practice.' I just feel like this particular show is its own animal. ... If it's a calm day, we're suspicious."