Child abuse is associated with markedly elevated rates of major depression (MDD) in child,adolescent, and adult cohorts. This article reviews preclinical (e.g., animal) studies of the effectsof early stress and studies of the neurobiological correlates of MDD in adults and children, and ithighlights differences in the neurobiological correlates of MDD and stress at variousdevelopmental stages. The preclinical studies demonstrate that stress early in life can alter thedevelopment multiple neurotransmitter systems and promote structural and functional alterationsin brain regions similar to those seen in adults with depression. Preclinical and clinical studiessuggest, however, that long-term neurobiological changes associated with early stress can bemodified by familial/genetic factors, the quality of the subsequent caregiving environment,and pharmacological interventions. Little is known about how developmental factors interact withexperiences of early stress and these other modifying factors. Moreover, in cases of childmaltreatment, the effects of early abuse are often exacerbated by failures in the child protectionsystem and repeat out-of-home placements. Given the number of factors that impact on thelong-term outcome of maltreated children, multidisciplinary research efforts are recommended toaddress this problem—with foci that span from neurobiology to social policy.