Despite the prevalence of the mood disorders, the underlying neuropathology is still poorly understood. This article describes abnormalities in brain activation that have been reported in neuroimaging studies of patients with depression and bipolar illness. Functional changes have been identified in regions important for neural networks underlying emotional processing, including frontal, subcortical, and limbic regions. The interpretation of neuroimaging studies in mood disorders is limited by potential confounding factors including medication effects, duration of illness, comorbidity, and gender.