Selective serotonin re-uptake inhibiting drugs (SSRIs) are widely used for endogenous depression. In addition to depleting the nerve terminals of serotonin they also lower blood platelet serotonin levels. Platelet aggregation is a major component of acute coronary syndromes, including sudden death, and also of limb ischaemia. Platelet-released serotonin causes constriction of diseased blood vessels. The recent literature has revealed a number of reports of association between the treatment of depression with SSRIs and reduced events caused by intra-arterial thrombosis. The effects of serotonin and serotonin depletion upon intracoronary thrombosis, diseased blood vessels, blood platelets and bleeding are discussed with recommendations for future research into the potential cardiovascular benefits of SSRIs and serotonin 5HT2A antagonists.