This article summarizes the epidemiology, clinical features, and treatment of antepartum and postpartum major depression. This summary will enable primary care clinicians to recognize and screen for perinatal mood disorders and to initiate the risk-benefit decision-making process used in treatment selection. This review will also help identify patient factors that warrant psychiatric consultation. We selected and reviewed studies of antepartum and postpartum depression of greatest utility to primary care clinicians. We developed a graphical algorithm that summarizes the steps needed for the care of postpartum depressed women. The prevalence of postpartum depression ranges from 10% to 15%, with screening rates of depressive symptoms as high as 35% in African American women. The prevalence of antepartum depression is as high as 26% among women in poor, urban communities. Maternal depression is associated with adverse effects on fetal and infant development. The challenge of diagnosing perinatal major depression can be addressed by assessing for persistent cognitive and affective symptoms and functional impairment. Effective treatments include interpersonal psychotherapy and selective serotonin reuptake inhibitors. The treatment of perinatal depression requires a unique informed consent process that is guided by a discussion of maternal preferences, the severity of maternal illness and recommended treatment, the risks of psychotropic exposure, and the risks of untreated mental illness. Rapid and effective mental health intervention in depressed expectant or new mothers not only restores maternal function, but can also prevent adverse infant neurobehavioral outcomes.