Postpartum depression strikes nearly one in five new mothers. Stress is a significant risk factor for this complex condition. Neuroscientists have generated a novel preclinical model of postpartum depression and demonstrated involvement of the hypothalamic-pituitary-adrenal axis (the neuroendocrine system that mediates physiological response to stress and is normally suppressed during and after pregnancy). These findings in mice provide the first empirical evidence that disruption of this system engenders behaviors mimicking human postpartum depression.