The cast of <EM>ER</EM> The cast of ER

Even for ER (premiering Thursday, Sept. 25 at 10 pm/ET, NBC), the send-off of rock-and-roll doc Ray Barnett (Shane West) a couple seasons back was disquieting (and this in a show that dispatched one character via falling helicopter). Drunk and reeling from his unrequited love affair with one-time roommate Neela (Parminder Nagra), Barnett lost both legs after a close encounter with a truck. "That was a shock to everybody," Nagra says. "Most of all Shane, I think."

So just imagine the reaction when Ray comes walking back this October. Clearly, ER, in its 15th and final season, has no intention of going out quietly. The season premiere picks up from last season's cliff-hanger, in which doctors Pratt (Mekhi Phifer) and Abby (Maura Tierney), along with nurse Sam (Linda Cardellini), were well within body-bagging distance of an exploding ambulance. Think ER wouldn't kill 'em off? Rumors have Phifer, Tierney and Goran Visnjic (Luka) leaving the show early.

The only thing certain, says exec producer David Zabel, is that by Episode 2, there'll be five new cast members. "Angela Bassett comes in very strong as the new chief of the ER, Cate Banfield," Zabel says. "Her backstory is going to involve being haunted by things from the past." Four new interns will be played by Victor Rasuk (Lords of Dogtown), Emily Rose (Brothers & Sisters), Shiri Appleby (Roswell) and Julian Morris (Cry Wolf). And in one of the more intriguing bits of casting, Courtney B. Vance, Bassett's real-life husband, will join the cast later this season playing, yes, her husband.

But even that might get overshadowed as the show hopes to recruit some series veterans for one last hurrah. (We'd suggest not getting your Clooney hopes up too high, though). Noah Wyle's Dr. Carter is already signed on for four appearances, and West's Ray walks back (on prosthetic legs) during a Halloween episode. Says Nagra, "Ray comes back at a time when Neela needs some direction."

And what of John Stamos? Is he in line for one of ER's patented send-offs?

"Well, I guess it depends on how I behave this year," Stamos jokes, "but I don't think they're gonna kill me off. There's gonna be nobody left for the last episode!"