In comparison with the vast epidemiological literature on postpartum depression (PPD), relatively few studies have examined the biological aspects of the disorder. However, research into the biological mechanisms of PPD is a challenging task, as normal pregnancy and the postpartum period cause adaptive endocrine changes, which would otherwise be considered pathological in nonpregnant women. This review focuses on the adaptive changes of childbearing and nursing, which ultimately may put women at increased risk of PPD. In light of the normal physiology, the authors also attempt to describe the current evidence of the biological changes associated with the development of depression in the postpartum period, including ovarian steroids, the hypothalamic–pituitary–adrenal axis, the serotonergic neurotransmitter system, the thyroid system and inflammatory markers. In addition, current knowledge on candidate genes associated with PPD is reviewed.