This chapter describes the epidemiology of drug use among adolescents from different racial and ethnic groups. Second, it addresses the cultural variables prevalent in each of these groups and their relevance in the delivery of clinical care. Third, it describes the risks and protective factors for adolescent drug use and their interface with culture and the screening tools available for the pediatrician. Finally, we present the treatment and model programs of prevention that were tested specifically with ethnic groups ranked by the National Registry of Evidence-Based Programs.