In 1983, Stein was diagnosed with pemphigus vulgaris, a rare autoimmune disease of the skin, but he has since regained normal function. Stein had contracted a mild form of the disease, and was able to control it with a program of steroids. As of 2011, he was still touring and recording with Blondie.
Stein is Jewish, and was born to Jewish parents in Brooklyn, New York. While in Blondie, Stein and Harry maintained a romantic relationship but never married. In 1989, the couple went their separate ways but have continued to work together on a professional basis. Stein was co-host of TV Party a public-access television cable TV show in New York City that ran from 1978 to 1982.
In 1999, Stein married the actress Barbara Sicuranza, and they have two daughters.