This article focuses on the concepts of risk and resilience and their potential to inform clinical interventions, school-based prevention programs, and social policies. Research suggests that childhood adversity can trigger a cascade of psychological and neurobiological events that can lead to mental disorders in later life. Yet little is known about how these processes manifest in adolescence, a developmental window that is typically associated with an elevated risk for psychopathology and represents a period of neurological growth and reorganization that is second only to early childhood. A better understanding of adolescent brain development may provide an empirical grounding to improve the focus and timing of interventions, particularly those that target self-regulation, meta-cognition, and social supports. Finally, opportunities and challenges that emerge when bridging neuroscience and prevention science are discussed.