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Purpose: Recent advances in developmental neuroscience have the potential to significantly impact the behavioral and academic outcomes of adolescents. By adopting a translational approach, we aim to promote the transfer of knowledge related to neurological, cognitive, and emotion regulatory factors that underlie youth's ability to respond to educational and prevention programming. Method: This article synthesizes basic and applied research from the field of developmental neuroscience to highlight the significance of this work for the creation, evaluation, and tailoring of school-based preventive interventions designed to address aggressive behavior problems. We draw on research related to stress, social-cognitive factors, emotional perception and regulation, and executive functioning to identify potential neurodevelopmental mediators and moderators of prevention program impacts. Results: Findings suggest that a high level of brain plasticity characterizes early childhood and adolescent stages of development, providing optimal windows of opportunity for intervention. The available research emphasizes the importance of executive functioning and related emotional regulatory factors as potential mechanisms for change in educational and risk prevention models. Conclusions: Neuroscience research provides insights into underlying mechanisms that, when appropriately targeted, can help optimize the impact of social-emotional learning curricula. Recommendations are made for how to apply relevant findings from neuroscience and related disciplines to improve behavioral and academic outcomes for school-aged youth. Additional research areas are identified to inform the creation of neurodevelopmentally sensitive preventive interventions targeting aggressive behavior problems which, in turn, are expected to affect academic outcomes. (C) 2012 Society for Adolescent Health and Medicine. All rights reserved