This review presents findings from an overview of meta-analyses of the effects of prevention and promotion programs to prevent mental health, substance use, and conduct problems. The review of 48 meta-analyses found small but significant changes that reduce depression, anxiety, antisocial behavior, and substance use. Furthermore, the results were sustained over time. Meta-analyses often found that the effects were heterogeneous. A conceptual model is proposed to guide the study of moderators of program effects in future meta-analyses, and methodological issues in synthesizing findings across preventive interventions are discussed.