Depression in patients with coronary artery disease is associated with increased cardiovascular morbidity and mortality. It is not clear, however, if treatment with selective serotonin reuptake inhibitors (SSRIs) decreases the rate of future cardiovascular events. This paper reviews the available literature regarding the effect of SSRI use on cardiovascular outcomes. Thirteen studies addressing this issue were identified. Of these, 5 concluded that SSRI use is associated with decreased cardiovascular morbidity or mortality, 2 concluded that SSRI use was associated with worsened prognosis, and 6 studies found no statistically significant association. Almost all of the published literature examining the effect of SSRIs on cardiovascular outcomes is based on observational studies, thereby precluding definitive conclusions. Randomized controlled studies are clearly needed to definitively address this issue.