The high prevalence of drug abuse, delinquency, youth violence, and other youth problems creates a need to identify and disseminate effective prevention strategies. General principles gleaned from effective interventions may help prevention practitioners select, modify, or create more effective programs. Using a review-of-reviews approach across 4 areas (substance abuse, risky sexual behavior, school failure, and juvenile delinquency and violence), the authors identified 9 characteristics that were consistently associated with effective prevention programs: Programs were comprehensive, included varied teaching methods, provided sufficient dosage, were theory driven, provided opportunities for positive relationships, were appropriately timed, were socioculturally relevant, included outcome evaluation, and involved well-trained staff. This synthesis can inform the planning and implementation of problem-specific prevention interventions, provide a rationale for multi-problem prevention programs, and serve as a basis for further research.