Serrano began his acting career in off-Broadway plays in the late 1970s. He often portrays authority figures on both sides of the law. His first film was the 1986 Tom Hanks comedy The Money Pit. Since then, he has appeared in supporting roles in films such as Lethal Weapon 2, Bad Boys, The Negotiator, Empire, The Insider, Runaway Jury and The Day After Tomorrow. He also has an extensive television résumé, with appearances in shows such as Burn Notice, Homeland, Alias, Blue Bloods, Law & Order, and its spin-offs, SVU and Trial by Jury.
In 2017, he played a Psychiatrist, Dr. Saul, in the movie thriller, Clinical.
