Gender differences in the epidemiology, comorbidities, and treatment responses of substance abuse have been described in adults. However, a growing body of data suggests that gender differences also exist in adolescents with substance abuse. Unfortunately, research is still limited in this age group. This article reviews gender differences in the diagnosis, presentation, course of illness, and treatment response of substance abuse in adults and adolescents. Adolescent substance abuse treatments that take into account these gender differences are also discussed.