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Adolescence is a critical growth period in which youth develop essential skills that prepare them for adulthood. Prevention and intervention programs are designed to meet the needs of adolescents who require additional support and promote healthy behaviors and outcomes. To ensure the success of these efforts, it is essential that they include reliably identifiable techniques, strategies, or practices that have been proven effective. Promoting Positive Adolescent Health Behaviors and Outcomes: Thriving in the 21st Century identifies key program factors that can improve health outcomes related to adolescent behavior and provides evidence-based recommendations toward effective implementation of federal programming initiatives. This study explores normative adolescent development, the current landscape of adolescent risk behavior, core components of effective programs focused on optimal health, and recommendations for research, programs, and policies.