Prevention of substance use disorders Abstract.Adolescence is a vulnerable period for the development of Substance Use Disorders and preventive intervention is a public health priority. In this article, we summarize the available evidence for behavioral preventive action for Substance Use Disorders and related dysregulated behaviors during adolescence in various settings.Current meta-analytic evidence is available mainly for the school and family settings and increasingly also for internet-based prevention. The literature is dominated by US-studies that focus on universal school-based approaches for legal substances in middle adolescence. Only few German studies are published. Taken together the results indicate that developmentally sensitive substance use prevention is effective across different settings with consistent small-to-middle sized effects. Differential effectiveness analyses for schoolbased prevention suggest that younger adolescents benefit most from universal prevention, while for older adolescents targeted approaches are more effective.Across the relevant settings, effective preventive measures are available. However, the results could be improved. There is a need for translational research on effective and more individualized approaches to prevention and differential effects of intervention modules. Moreover, there is a need for research on the implementation of evidence-based programs and especially in Germany, coordinated approaches on community levels are lacking.