Born the son of a grocer in new York, Picano was educated at Queens College of the City University of New York, and traveled to Europe. He settled in Greenwich Village in the early 1960s, and had a varied career, as a social worker in East Harlem, New York, assistant editor and bookstore manager, before venturing into freelance writing. He was a founding member of the Violet Quill club, a group of young gay writers in New York in the 1970s.

Picano has been active in gay politics and in gay publishing. He has published some twenty books renging from thrillers such as The Lure, to self-help books, such as The New Joy of Gay Sex. His books have charted gay life in the US over the past few decades.