Stress can have lasting effects on the brain and behavior. Delineating the impact of stress on the developing brain is fundamental for understanding mechanisms through which stress induces persistent effects on behavior that can lead to psychopathology. The growing field of translational developmental neuroscience has revealed a significant role of the timing of stress on risk, resilience, and neuroplasticity. Studies of stress across species have provided essential insight into the mechanisms by which the brain changes and the timing of those changes on outcome. In this article, we review the neurobiological effects of stress and propose a model by which sensitive periods of neural development interact with stressful life events to affect plasticity and the effects of stress on functional outcomes. We then highlight how early-life stress can alter the course of brain development. Finally, we examine mechanisms of buffering against early-life stress that may promote resilience and positive outcomes. The findings are discussed in the context of implications for early identification of risk and resilience factors and development of novel interventions that target the biological state of the developing brain to ultimately ameliorate the adverse consequences of stress during childhood and adolescence.