Born in Greenwich Village, New York, McGinley's love for acting began as an undergraduate at New York University. In 1984 he received a masters of fine arts degree from the prestigious New York University theater school. His first big break in theater came when he took over the role played by actor John Turturro in the Circle in the Square's Danny Deep Blue Sea. He went on to perform in numerous theatrical productions, including Requiem for a Heavyweight on Broadway, and off-Broadway in The Ballad of Soapy Smith and Talk Radio, both at Joseph Papp's renowned Public Theater.

McGinley has also had an impressive career in film, portraying a diverse range of characters. He has appeared in over 50 feature films, which include The Animal, Any Given Sunday, The Rock, Nothing To Lose, Set It Off, Seven, Office Space, Wall Street and Platoon. He has also served as producer on a number of films, including Colin Fitz and Watch It, Identity, Stealing Harvard, Wild Hogs, 42, Kid Cannabis, Get a Job, The Belko Experiment, Battle of the Sexes, The Good Catholic, and Benched.

On television he starred in the highly-rated Dean Koontz miniseries Intensity. He also starred in and produced the television movie The Jack Bull. He is well known for his role as Dr. Perry Cox on the long-running comedy Scrubs. He also had a recurring role on Burn Notice. He has also had important roles in Ground Floor, Stan Against Evil, and Chicago PD.

McGinley resides in Los Angeles and enjoys surfing, weightlifting, golf and softball. As the father of a son with Down syndrome, he is committed to building awareness and acceptance of people with Down syndrome. In 2006, McGinley served as the national spokesperson for the National Down Syndrome Society's annual Buddy Walk. He serves on the Board of the Global Down Syndrome Foundation, based in Denver. He is a celebrity Ambassador for the National Down Syndrome Society. In addition, he is a Global Ambassador for Special Olympics and was an integral part in crafting its "R-word: Spread The Word, To End The Word" campaign. McGinley is a vocal supporter for the special needs community.

In 2005, he wrote a book titled Untalkative Bunny: How to be Heard Without saying a Word.

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