Cardiovascular disease is the leading cause of mortality in women costing more than 500,000 lives each year in the United States alone. Major depression in healthy subjects increases cardiovascular mortality in both men and women. The presence of major depression in patients with recent acute myocardial infarction (AMI) or unstable angina more than doubles the risk of cardiac death in both men and women. In the presence of depression, lack of social integration has an additive effect on cardiac events. Depression is more prevalent in women with coronary heart disease (CHD) than in men. Psychologic counseling as well as cognitive behavioral treatment in women post-AMI seems to adversely affect prognosis, whereas it has neutral effects in men. Pharmacologic treatment of depression with serotonin reuptake inhibitors is safe in men and women post-AMI and is particularly effective in patients with recurrent depression. Whether effective treatment of depression lowers cardiac mortality remains to be proven.