But the actress truly seemed to hit her stride in her 30s, racking up an Emmy-winning guest stint as Jennifer Aniston's younger sister on "Friends" (2002-03); a Tony nod as the title character in "Sweet Charity" on Broadway; and a couple Emmy nominations for playing a recovering amnesiac on "Samantha Who?"
When it comes to big-screen comedy, Applegate has proved equally adept. She stepped as Cameron Diaz's best friend in The Sweetest Thing (2002) and also played the straight woman to an outrageous Will Ferrell in Anchorman: The Legend of Ron Burgundy (2004).