Recent technological advancements have facilitated the study of adolescent neurological development and its implications for adolescent decision-making and behavior. This article reviews findings from the adolescent neurodevelopment and substance use prevention literatures. It also discusses how findings from these two distinct areas of adolescent development can complement each other and be used to build more developmentally appropriate interventions for preventing adolescent substance use. Specifically, a combination of child-centered and family-based strategies is advocated based on extant neurological and prevention literature. EDITORS' STRATEGIC IMPLICATIONS: Researchers are encouraged to take up the authors' challenge and study the links between adolescent neurological development/decision making ability and the long term efficacy of comprehensive interventions for preventing adolescent substance use.