Adolescent behavior problems such as substance use, antisocial behavior problems, and mental health problems have extremely high social costs and lead to overburdened mental health and juvenile justice systems in the United States and Europe. The prevalence of these problems is substantial, and at-risk youth often present with a combination of concerns. An understanding of risk and protective factors at multiple levels, including the child, family, peer, school, and community, has influenced intervention development. At the individual and family levels, the most effective and cost-effective programs work intensively with youth and their families or use individual and group cognitive-behavioral approaches. However, there is a paucity of careful studies of effective policies and programs in the juvenile justice system. Research is needed that focuses on adoption, financing, implementation, and sustainable use of evidence-based programs in public service systems. In addition, the field needs to understand better for whom current programs are most effective to create the next generation of more effective and efficient programs.