A large and growing literature suggests that traumatic experiences early in life increase the risk of mood and anxiety disorders in genetically predisposed persons. Findings from laboratory animal studies as well as studies of women with histories of early-life trauma demonstrate that long-lived alterations in the corticotropin-releasing factor (CRF) system and stress responses underlie this vulnerability. Women with histories of abuse plus current depression exhibit the greatest abnormalities in the hypothalamic-pituitary response to stress and may represent a unique cohort of patients. Studies in laboratory animals also suggest that persistent changes in the CRF system may be reversed by antidepressants or surrogate parenting, which underscores the urgent need for primary and secondary prevention studies in children who are living in adverse or dangerous environments. Psychopharmacology Bulletin. 2004;38(Suppl 1): 14-20.