Adolescent sexual risk-taking behavior has numerous individual, family, community, and societal consequences. In an effort to contribute to the research and propose new directions, this chapter applies the core competencies framework to the prevention of high-risk sexual behavior. It describes the magnitude of the problem, summarizes explanatory theories of high-risk sexual behavior, and highlights the association between high-risk sexual behaviors and the five core competencies. We conclude the chapter by providing an overview of selected evidence-based prevention strategies and identifying future directions for research and intervention.