This review summarizes current research regarding the role of the frontal lobe in the pathophysiology of affective disorders, focusing on the following domains: neuropathology, neuropsychological functioning, functional neuroimaging, electrophysiology, and structural neuroimaging. Parallels between the symptomatology of frontal lobe impairment and that of manic and depressive episodes are delineated. The specific mechanisms by which the frontal regions influence affective symptoms are far from clear, yet there is significant data to support a correlation between frontal lobe changes and the affective, behavioral, and cognitive changes exhibited in both bipolar and unipolar disorders. Although affective symptomatology cannot be specifically localized to the frontal lobe, data from diverse sources suggest that this brain region may play a central role in more complex neural circuits associated with affective syndromes, particularly in its regulatory capacity.