Depression in patients with acute coronary syndromes (ACS) is common and associated with impaired cardiovascular prognosis in terms of cardiac mortality and new cardiovascular events. It remains unclear whether antidepressant treatment may reverse these effects. In this review, the literature is evaluated on (i) the antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) for depression in patients with ACS; (ii) the pleiomorphic effects of SSRIs that may be associated with cardiovascular prognosis; and (iii) the effects of SSRIs on cardiovascular prognosis.SSRIs provide modest relief of depressive symptoms in selected subgroups of depressed patients with ACS. With respect to the pleiomorphic effects of SSRIs, three mechanisms of how SSRIs may improve cardiovascular prognosis are discussed: via platelet function, via the autonomic nervous system (ANS) and via vasomotor tone. Some studies show that SSRIs may reduce platelet activity and sympathetic nervous system activation, but results are inconclusive. SSRIs are associated with vasodilation but this needs to be confirmed with in vivo experiments. Some non-experimental studies describe favourable effects of SSRIs on cardiovascular prognosis. Despite recent developments, much of the effect of SSRIs on cardiovascular prognosis remains unclear. Although some studies suggest effects of SSRIs on platelet function, ANS and vasomotor tone, which may lead to improved cardiovascular prognosis, results are largely inconclusive. More well designed studies addressing these questions are needed. Moreover, since the effects of SSRIs on depression itself are limited, efforts should be dedicated to study the diagnostic validity and homogeneity of depression in the context of ACS and the presence of clinically relevant subtypes.