Nearly 10% of Latino youth who are twelve and older are in need of substance abuse treatment for alcohol or illicit drug use. Ethnic differences exist with regard to susceptibility to drug use, attitudes regarding drugs, and drug resistance strategies. The failure of some substance abuse prevention programs can be traced in part to their lack of cultural sensitivity. This article reviews substance use patterns of Latino youth, presents some unique culturally-based factors that should be considered in clinical work with Latino youth, and then reviews two culturally-sensitive intervention strategies that have been tested with this unique population (Familias Unidas and Brief Strategic Family Therapy).