1. Emotion and mood, once thought to be governed solely by the limbic system of the brain, now are thought to be influenced by numerous nonlimbic central nervous system structures as well. 2. The present review discusses several important brain structures and neuroanatomic pathways thought to be involved in affect and mood disorders, including the amygdala, frontal neocortex, cingulate gyrus, basal ganglia, and the monoamine systems. 3. The authors propose a specific neuroanatomic model for depression that emphasizes that a distributed system of extensively interconnected CNS structures mediates emotion and affect.