He is best known for his character roles such as Sam Gorpley on Perfect Strangers, Principal Willis DeWitt on Growing Pains, Holland Manners on Angel, dentist Bernard Nadler on Lost, Doctor Harad in Friends, and in film, as the principal in Forrest Gump.

Anderson is best known for his roles as mailroom supervisor Mr. Gorpley on Perfect Strangers,[6] Mike Seaver's adversarial Principal DeWitt on Growing Pains, a chief of Cardiology on ER, the lawyer Holland Manners on the first two seasons of Angel[7] and as Bernard on Lost.

His other guest-starring roles include Remington Steele, Hill Street Blues, The Golden Girls, Murder, She Wrote, Picket Fences, The West Wing, Everybody Loves Raymond, and many other shows.

Anderson guest-starred in Season 8 of NCIS as Walter Carmichael, a middle school teacher whose classroom becomes a crime scene where one of his students is kidnapped.

He plays the husband (Edwin) of Kathy Bates character Matty Matlock.