Advances in prevention science in the past 25 years provide important direction for neighborhood and community efforts to improve the lives of youth. Prevention scientists have applied a public health approach to youth problems such as drug use and delinquency, and have shown that these problems can be prevented. The identification of risk and protective factors for adolescent health and behavior problems provides the foundation for advances in this field, and prevention scientists have rigorously tested programs and policies that address these risk and protective factors. Communities That Care is a prevention operating system that provides tools to guide coalitions in recent scientific advances to promote measurable change for children and youth in the community. This article describes Communities That Care system, its research foundation, and evidence of its effectiveness at the community level.