This paper 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 effects to reduce depression, anxiety, anti-social behavior and substance use. Further, the effects are 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.