Look Who's Turning 40 and 50

This brilliant sketch artist (starting her third season of Tracey Ullman’s State of the Union on Showtime January 25) excels at playing everyone from Renée Zellweger to Laura Bush. A Brit who has lived in the U.S. for 20 years, she became an American citizen in 2006 so she’d be able to vote.

An ethereal French beauty best known for Before Sunrise and Before Sunset, Delpy has been acting for 30 years. She made her feature-directing debut with 2 Days in Paris and called directing a “good kind of stress,” one that makes her feel “invincible.”

Her Emmy-winning role on The West Wing notwithstanding, Janney tells MORE that “I definitely like to play crazy characters. I like to find what I love about them. And what breaks my heart about them.”

Pompeo and husband Chris Ivery welcomed their first child, daughter Stella, in September. Last year, she told Allure that she packed in a lot of living first because she knew parenthood would be a huge change.“So when I have the baby, I won’t feel like we’ve missed any fun, reckless times together, like staying up all night drinking champagne and having sex until five in the morning and not having to get up until two in the afternoon.” That’s planning ahead!

As strong and sexy as when she first hit the hip-hop scene, she’s a woman who has no interest in being taken for a girl.

The Duchess of York—a.k.a. the first Fergie—is a champion reinventor, becoming both a weight-loss spokeswoman and a best-selling children’s book author after her royal marriage dissolved.

As “Stacy’s Mom,” she had it goin’ on. At 40, this New Zealand-born model still does.

Our favorite C Z-J moment? Accepting her Oscar—even performing a song—while very pregnant, with style to spare.

The woman who, as Grey’s Anatomy’s inimitable Dr. Bailey, officially introduced vajayjay to the lexicon is someone we’re thrilled to have on our team.

“I want a big rock concert for my fiftieth birthday,” the actress (and inspiration for the Toto song “Rosanna”) told MORE last year.

She’s got an Oscar, a Tony—and now a milestone birthday to celebrate!

J.Lo, Jenny From the Block—whatever the moniker, she’s right up there with Madonna as a mother of reinvention.

The singer-songwriter, a longtime member of Amnesty International, has had hits such as “Luka” and “Tom’s Diner” covered and remixed by other influential artists.

What would House do to celebrate a milestone birthday like Laurie’s? Probably alienate his patients, fantasize about Cuddy and treat himself to a few extra painkillers. Pretty much like any other day, then. We’re sure Laurie has something much less misanthropic planned.

Since her retirement 10 years ago, this tennis champion—called the greatest female player of all time by Billie Jean King—now focuses on her two kids (with husband Andre Agassi) and the charity she founded, Children for Tomorrow.

Not only is the NBC Nightly News anchor smart and reassuring, but he was one of the best Saturday Night Live hosts in years. Who could ask for more?

The rapper/actor/producer is reportedly working on a big-screen adaptation of Welcome Back, Kotter. From gangstas to Sweathogs in 20 years—who’d have thunk it?

She has played Elizabeth I, Katharine Hepburn and Bob Dylan. With all that history under her belt, it’s about time she turned 40.

If her personal life has been a bit of a soap opera, well, she did start out on Another World. But who cares? She’s always riveting.

NEXT: View a slideshow of Second-Generation Stars here