This Review summarizes many of the persistent biological alterations associated with childhood maltreatment including changes in neuroendocrine and neurotransmitter systems and pro-inflammatory cytokines in addition to specific alterations in brain areas associated with mood regulation. Finally, I discuss several candidate gene polymorphisms that interact with childhood maltreatment to modulate vulnerability to major depression and PTSD and epigenetic mechanisms thought to transduce environmental stressors into disease vulnerability. Neuron Review, vol. 89, March 2, 2016 pp.892-909