Postpartum mood disorders are common. The clustering of mood-disorder episodes after birth compels a search for factors particularly potent during childbearing. In this article, the complex relationships between the dynamic postbirth physiological environment and mood disorder are discussed. Available studies show a lack of evidence that serum levels of gonadal hormones account for mood disturbance in women. However, substantial amounts of data demonstrate their ability to modulate other neuroendocrine systems. Alterations in hypothalamic-pituitary-adrenal (HPA) axis function attributable to childbearing show remarkable similarity to those observed in depressed women. Postpartum women are also at increased risk for hypothalamic-pituitary-thyroidal (HPT) axis dysfunction that may increase affective-disorder vulnerability. A decreased rate