At 12, Dempsey is diagnosed with dyslexia. "I think that's when I get most insecure," he tells Barbara Walters of reading scripts in 2006. "It's very hard for me to read off the page. I need to memorize it in order to go on." At 17, he leaves high school in Lewiston, Maine to pursue acting and wins the role of David in a San Francisco production of Torch Song Trilogy.
Playing the loveable dork in the teen comedy Can't Buy Me Love puts Dempsey on the Hollywood hot list and wins him adoring fans. "I get a lot of people who confess childhood crushes on me," he tells PEOPLE in 2006. "That makes a guy feel good about himself."
At 21, Dempsey marries his manager Rocky Parker, who is 27 years his senior and the mother of his best friend. Seven years later, the couple divorces. "Yeah, I think I needed a mother," Dempsey admits to Barbara Walters in 2006.
Dempsey stars as a pizza boy who delivers more than just pies to older women in the comedy ''Loverboy". He admits he didn't know how to deal with fame at such a young age. "You can't have temper tantrums," Dempsey says in 2006. "You have to be professional, and I don't think I understood that at the time." In 1991, he stars opposite Christian Slater in the critically panned Mobsters. Entertainment Weekly calls Dempsey and his costars "too fundamentally carefree to be interesting actors." His once hot career begins to cool off.
Dempsey's first major film in three years, the collegiate comedy With Honors, isn't enough to raise his grade. "I wasn't on the hot list anymore," he later tells PEOPLE.
After years of flirting during haircuts, Dempsey marries Jillian Fink, a hairstylist and makeup artist. When he sees his bride coming down the aisle, he cries. Months later, things continue to look up as Dempsey appears in a supporting role in Scream 3.
Dempsey makes memorable guest appearances as Eric McCormack's love interest on Will & Grace and Sela Ward's mentally ill brother on Once and Again. His work on Once and Again is recognized with an Emmy nomination for Outstanding Guest Actor in a Drama Series.
The actor and his wife welcome their first child, Talula Fyfe. "I have a loving wife and healthy daughter and at the end of the day that's what it's about," he later tells The Philadelphia Inquirer.
Dempsey jumps back on Hollywood's radar as Reese Witherspoon's charming fiancé in Sweet Home Alabama. Once again Dempsey is considered leading man material. Of his second time around with fame, he tells PEOPLE, "I really love it now, but I also have a life outside it with Jill and Talula."
Mid-season replacement Grey's Anatomy becomes the surprise hit of the year. Dempsey's Dr. Derek Shepherd gets viewers' pulses racing and makes him a star. . . again. "The phone rings a lot more than it used to," he tells Entertainment Weekly. "People are really enthusiastic and warm to you, as opposed to when a movie comes out and it's crap."
BIOGRAPHY (top to bottom): David Libby/Bauer-Griffin; Touchstone Pictures/Everett; DMIPhoto; Paul Smith/Featureflash; Everett Collection; A. Turner/J. Louis/Splash News; Everett Collection; Frank Ockenfels/ABC