Depression during pregnancy and in the postpartum period is common, devastating to mothers and their offspring, and poorly understood in terms of pathophysiology. In this issue of Neuron, Maguire and Mody provide evidence for a role for aberrant neurosteroid regulation of the GABA(A) receptor subunit in the etiology of postpartum depression, presaging elucidation of the pathophysiology and development of treatments of this depression endophenotype.