He had a recurring role as Andy Sparks in the TV series Chicago Hope from 1998 to 1999. Louiso has starred in the films Stella, Billy Bathgate, Scent of a Woman, Apollo 13, The Rock, Jerry Maguire, Eight Heads in a Duffel Bag, A Cool, Dry Place, Thank You for Smoking, Snakes on a Plane, School for Scoundrels, Meet Bill, A Bag of Hammers, and The Switch. Louiso has directed the films Love Liza, The Marc Pease Experience, and Hello I Must Be Going. His films Love Liza and Hello I Must Be Going were both nominated for a Grand Jury Prize at the Sundance Film Festival.