Recent studies have uncovered more and more evidence demonstrating the adverse relationship between depression and ischemic heart disease. One of the most significant mechanisms that may explain the adverse relationship is the increased platelet activity, otherwise known as aggregation, observed to occur in patients with depression or ischemic heart disease. Platelet activity is further elevated in patients with depression and ischemic heart disease. Selective serotonin reuptake inhibitors are antidepressants and also act like platelet inhibitors. The results of large-scale clinical trials suggest that the use of selective serotonin reuptake inhibitors may reduce cardiac events in post-myocardial infarction patients or in those with unstable angina that may be related to the effects of selective serotonin reuptake inhibitors on platelet aggregation.