Alex O'Loughlin was best known as the blood-sucking P.I. on CBS' Moonlight. Fans can see their beloved Aussie getting his hands bloody again this fall. Only this time he'll play Dr. Andy Yablonski, the leader of a team of surgeons at a transplant hospital.

Besides being a singer, the younger sister of Jessica Simpson, and the wife of Fall Out Boy's Pete Wentz, she also played Cecilia on the squeaky clean 7th Heaven. This fall the pop rocker will move into the newly renovated Melrose Place as small-town girl Violet Foster.

Barton will always be remembered from her The O.C. role as Marissa Cooper, Ryan's on-and-off girlfriend. This fall, the starlet hits the Ashton Kutcher-produced series The Beautiful Life, which revolves around a group of models sharing a residence in New York.

Margulies trades the emergency room for the court room in her new CBS drama, in which she plays the wife of a politician (Chris Noth) who pursues her own career as a defense attorney after her hubby's indiscretions land him in jail. Margulies, who won an Emmy for her stint on ER, has played a lawyer before — on Fox's short-lived Canterbury's Tale. Now, how can we get George Clooney to drop by?

You most likely remember him as dysfunctional dad Al Bundy from the long-running series Married... with Children. O'Neill is back for yet another hilarious, family-focused sitcom, Modern Family. He's joined by Bowen, who's bounced all over the small screen but is best known for her roles as high school English teacher Carol Vessey on Ed and attorney Denise Bauer on Boston Legal. She plays a frazzled housewife and mom of three, as part of the most normal family unit on the show. But that's not really saying much

No more twentysomethings in a purple apartment! The Friends and Dirt alum has graduated to cougar status on the new ABC sitcom, playing a 40-year-old, on-the-prowl single mom raising her own near-twentysomething. Could she be any hotter?

LL is best known for his rhymes, but he also starred in the NBC/UPN sitcom In the House and several movies. Following a guest arc on Grey's Anatomy, O'Donnell moves from the big screen (Scent of a Woman, Batman & Robin), to star as the enigmatic leader of an undercover NCIS unit. LL plays an ex-Navy SEAL and member of O'Donnell's unit.

Mr. Shakespeare In Love himself is moving to the small screen in ABC's highly anticipated drama, playing Mark Benford — an FBI agent who struggles to make sense of a global blackout that gave everyone a brief glimpse into the future. Joining him is a tough trauma surgeon played by Walger, who both brightened and broke our hearts as Desmond's long-lost lover, Penny, on Lost.

She'll forever be known as The Sopranos Adriana, but De Matteo also appeared in Joey and, most recently, Sons of Anarchy. This season, she gives network TV another go on Desperate Housewives as Wisteria Lane's newest import — direct from New York City. We can't wait for some new, tough-talking attitude to hit the suburbs.

Somerhalder is forever endeared to Lost fans as sacrificial lamb Boone Carlyle (R.I.P.), but you don't have to worry about him dying on his new show. He's already dead. In Vampire Diaries, he plays one of two vamp brothers who return to Mystic Falls, Va., to battle for a young high schooler's soul (and heart?).

He was the ever-so-slimy con man T-Bag on Prison Break, and she was the lusty, manuscript-stealing teenager on Californication. Both now on Heroes, one plays the season's big baddie and the other is Claire's college gal pal. We'll let you guess who's who.