Objective To identify differential treatment profiles between genders among adolescent substance abusers and make treatment recommendations based on those profiles, if identified. Method The sample included 137 adolescents in a residential treatment facility. Psychosocial Problems and problem behaviors were examined using a cluster analysis of 23 variables. When differential profiles were identified, the literature was reviewed for treatment implications. Results: Important implications for treatment based on the profiles were identified and discussed. Conclusions The current study suggests that treatment for adolescent substance abusers should have different characteristics for each gender. The findings have important implications for micro, policy, and research practitioners.