The significance of psychosocial stress and ways of coping with stress for understanding resilience in childhood and adolescence are reviewed. Psychological and biological processes of reactivity to and recovery from stress are central in understanding the physical and emotional tolls that result from prolonged exposure to chronic stress. A central theme of this article is that stress exerts a double toll on physical and emotional health and well-being. First, as a consequence of allostatic load, stress contributes to disease and disorder. And second, because of effects on specific brain regions, chronic stress takes a second toll by disrupting function in those regions primarily responsible for coping and self-regulation. Implications for future research on resilience and the development of interventions to promote resilience are highlighted.