Lesbian, gay, and bisexual (LGB) adolescents report disparate rates of substance use, and often consume more cigarettes, alcohol, marijuana, cocaine, and ecstasy than their heterosexual peers. It is therefore crucial to understand the risk factors for substance use among LGB adolescents, particularly those unique to their minority status. In an effort to organize the current knowledge of minority-related risk factors for substance use among LGB youth, this study presents results from a systematic review and meta-analysis of the published research literature. Results from 12 unique studies of LGB youth indicated that the strongest risk factors for substance use were victimization, lack of supportive environments, psychological stress, internalizing/externalizing problem behavior, negative disclosure reactions, and housing status. Results are discussed in terms of their implications for targeted intervention programs that address minority stress risk factors for substance use among LGB youth.