Single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies are yielding a picture of clinical depression as a disorder associated with dysfunction in specific brain regions. These data support the view of depression as a disease of the brain in general and of the frontal and temporal lobes in particular. Frontal lobe hypometabolism is emerging as a common final pathway for most types of primary and secondary depression, regardless of the original cause. The severity of depression is often related to the degree of frontal hypometabolism, and preliminary studies indicate that the hypometabolism normalizes after treatment in concert with the patient's improved mood. Primary depression also is associated with abnormal activation of key brain areas, including discrete aspects of the frontal and temporal lobes, the amygdala, and the cingulate gyrus. Several areas of research are currently under way using SPECT or PET to explore further the neuroanatomy of depression.