Epidemiological research over the past decade indicates that major depression and depressive symptomatology are common among patients with coronary artery disease (CAD) and postmyocardial infarction. Major depression is a serious, debilitating comorbid disorder that can significantly increase risk for and complicate recovery from cardiac events (eg, myocardial infarction). Unfortunately, major depression is rarely detected or treated in the cardiology setting. However, it is a disorder that can be successfully and safely treated in the majority of cases. Although the mechanisms that may be mediating the depression-CAD link are less well understood, there are several plausible mechanisms by which depression may influence the course and outcome of CAD. This review examines the literature linking major depression and depressive symptomatology to CAD course and outcome, and makes recommendations for improving assessment and treatment of depression in the cardiology setting.