Neuropsychological research provides a useful framework to study emotional problems, such as depression, and their correlates. This paper reviews several prominent neuropsychological theories. Functional neuroanatomical systems of emotion and depression are reviewed, including those that describe cerebral asymmetries in emotional processing. Following the review, a model that is composed of three neuroanatomical divisions (left frontal, right frontal, and right posterior) and corresponding neuropsychological emotional sequelae within each quadrant is presented. It is proposed that dysfunction in any of these quadrants could lead to symptomatology consistent with a diagnosis of depression. The proposed model combines theories of arousal, lateralization, and functional cerebral space and lends itself to scientific methods of investigation. Accordingly, research, prevention, and treatment programs in accordance with the proposed model may promote an improved understanding of the neuropsychological mechanisms involved in depression.