The pathogenesis of postpartum depression remains to be fully elucidated but likely results from the interactions of genetic factors, environmental influences, and the physiological demands of pregnancy, childbirth, and lactation. Epidemiological evidence and clinical findings suggest that low dietary and/or tissue levels of n-3 (omega-3) polyunsaturated fatty acids (PUFA) may be a factor contributing to the etiologies of both major depression and postpartum depression. Animal studies indicate that reproducing females are at particular risk of losing the n-3 PUFA DHA from tissues, including the brain. A decrease in brain DHA content causes a number of neurobiological effects that also occur in major depression disorder. This evidence, which supports the involvement of decreased brain n-3 PUFAs in the etiology of postpartum depression and other depressive disorders, and their implications for the prevention and treatment of these disorders, are discussed.