Selected studies with specific relevance to substance abuse prevention interventions with Hispanic youth and families were examined to identify prior findings and emerging issues that may guide the design of future substance abuse prevention intervention research and its implementation with Hispanic populations. The origins of prevention research and role of risk and protective factors are examined, including culturally-specific risk and protective factors for Hispanic populations. Correlational studies, non-experimental interventions, and randomized controlled trials were examined for the period of 1974-2003. The literature search yielded 15 articles selected for this review that exhibited adequate methodological rigor. An added search for more recent studies identified three additional articles, for a total of 18 prevention intervention articles that were reviewed. Theoretical and methodological issues and recommendations are presented for future research aimed at improving the efficacy and effectiveness of future prevention intervention studies and their cultural relevance for Hispanic populations.