Neuroimaging technology has been applied to investigate the pathophysiology of mood disorders in studies aimed at characterizing the anatomical correlates of depressive symptoms, the neurophysiological effects of antidepressant treatments, and the trait-like abnormalities that persist despite symptom remission. These studies have identified cerebral blood flow and metabolic differences between depressives and controls in the amygdala and anatomically related areas of the prefrontal cortex, striatum, and thalamus. Taken together with converging evidence from neuroendocrine, lesion analysis, and postmortem studies of clinically depressed subjects, these data suggest that emotional/stress-response systems that include the amygdala are pathologically activated in major depression and that this activity is associated with dysfunction of the prefrontal cortex and monoamine neurotransmitter systems that normally modulate such responses.