The psychological and neurological impact of cardiac surgery has been of keen empirical interest for more than two decades although reports showing the prognostic influence of depression on adverse outcomes lag behind the evidence documented in heart failure, myocardial infarction, and unstable angina. The paucity of research to date is surprising considering that some pathophysiological mechanisms through which depression is hypothesized to affect coronary heart disease (e.g., platelet activation, the inflammatory system, dysrhythmias) are known to be substantially influenced by the use of cardiopulmonary bypass. As such, cardiac surgery may provide a suitable exemplar to better understand the psychiatric mechanisms of cardiopathogenesis. The extant literature is comprehensively reviewed with respect to the deleterious impact of depression on cardiac and neuropsychological morbidity and mortality. Research to date indicates that depression and major depressive episodes increase major cardiovascular morbidity risk after cardiac surgery. The association between depressive disorders and incident delirium is of particular relevance to cardiac surgery staff. Contemporary treatment intervention studies are also described along with suggestions for future cardiac surgery research.