Although neutral-state functional neuroimaging studies have improved the understanding of the pathophysiology of major depression, studies that employ state manipulations may provide further information. Such interventions of the effects of acute or chronic pharmacologic treatment. This article has reviewed issues surrounding functional neuroimaging studies of treatment. Because the ultimate goal of psychiatric research is improved understanding of the pathophysiology as well as treatment of mental illness, the proposed contribution of these studies is the development of tests that will guide case management and thus be clinically useful.