Almost four decades of intensive research have sought to elucidate the neurobiological bases of depression. Epidemiological studies have revealed that both genetic and environmental factors contribute to the risk for depression. Adverse early-life experiences influence neurobiological systems within genetic limits, leading to the neurobiological and behavioral manifestations of depression. We summarize the burgeoning evidence concerning a pre-eminent role of early adverse experience in the pathogenesis of depression. The available data suggest that (1) early adverse experience contributes to the pathophysiology of depression, (2) there are neurobiologically different subtypes of depression depending on the presence or absence of early adverse experience, likely having confounded previous research on the neurobiology of depression, and (3) early adverse experience likely influences treatment response in depression. Classification of depression based on developmental and neurobiological features will likely considerably improve future research in the field of depression, and might lead to optimized treatment strategies that directly target different neurobiological pathways to depression.