He became popular as Dr. Derek Shepherd, or "McDreamy," on Grey's Anatomy and was nominated for a MTV Movie Award for Best Kiss for his role as Robert in 2007's Enchanted. In 2011, he played the character Dylan in the blockbuster film Transformers: Dark of the Moon.
He was diagnosed with dyslexia at age 12, so he had to memorize all his lines for auditions. During high school, he tied for second in a national juggling championship.
He played roles in the 2002 film Sweet Home Alabama and the 2008 film Made of Honor.
He co-starred with Ellen Pompeo on Grey's Anatomy.