Growing up as the son of an architect and an artist, his parents encouraged him to act at age 16, which eventually led him to attending a summer workshop in London before graduating from high school. Returning to the United States, Edwards worked in commercials, jobs that helped him pay his education at The University of Southern California where he studied acting. However, he dropped out of college, and in that same year, he had a small role in the movie Fast Times at Ridgemont High (1982), starring Sean Penn. The movie was a box office smash and Edwards was looking forward to doing more films.
His very first movie role was that of teen-aged John Muldowney in Heart Like a Wheel (1983), and his first starring role as nerdy Gilbert Lowell, in Revenge of the Nerds (1984). Edwards didn't need to worry about being typecast as a socially-challenged loser. After starring in The Sure Thing (1985) and Gotcha! (1985), he landed another big-time successful movie Top Gun (1986), in which he played Tom Cruise's ill-fated easy going navigator/best friend, Lt. Nick "Goose" Bradshaw. As Cruise rode "Top Gun" into the Hollywood stratosphere, Edwards also found his flight to stardom, at the same time. After "Top Gun", he reprized his role as Gilbert in the movie Revenge of the Nerds II: Nerds in Paradise (1987), before he starred in Summer Heat (1987). He also featured in Mr. North (1988), and Miracle Mile (1988), however they weren't too successful.
He began working in TV movies and continued to star in more box office movies such as Hawks (1988), How I Got Into College (1989), Downtown (1990), Pet Sematary II (1992), Landslide (1992) and Delta Heat (1992). The 90s won Edwards his best reviews for his recurring role of the quirky "bubble man" Mike Monroe on the immensely-popular "Northern Exposure" (1990). He was nominated for a Cable Ace Award in HBO's Sexual Healing (1993), and the following year, he starred in Charlie's Ghost Story (1994), before he played lawyer Clint Von Hooser in The Client (1994), which led him to the ultimate role of a lifetime, as easy-going charismatic physician, Dr. Mark Greene on "ER" (1994). For his work on "ER", he was nominated for an Emmy Award, 4 times For Outstanding Lead Actor in a Drama Series, but has never won, however, he has won a Golden Globe Award For Best Performance by an Actor-In a TV Series, and was nominated 4 times, and also has 2 Screen Actor's Guild Awards. Prior to playing Dr. Greene, he also played bank breaker turned cold-blooded killer, Dick Hickock in the TV movie remake of Truman Capote's In Cold Blood (1996) (TV), which was the best TV movie of the 1996-97 season. During his hiatus on "ER" (1994), he went back to the box office circuit to star and to produce the movie Don't Go Breaking My Heart (1999), which was a pretty complex movie, which wasn't a big hit.
Edwards, once again, returned to the set of "ER", and this time, he signed up for a salary that almost no actor could be paid, so his decision was to stay on the show for 3 more years and possibly to save the money in order to spend a lot of family time and to work on directing later. His first big roles after ER were that of Brains in the movie Thunderbirds (2004), and as Jim Paretta in The Forgotten (2004). In the many years that he starred on ER, that show gave him more success in working on and off the set, also it gave him a spiritual blessing that so many popular actors have had over the years.
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