Platelets are key players in thrombosis, and have thus become the main targets in the acute treatment of, as well as in the primary and secondary prevention against, thrombotic cardiovascular diseases. Three main classes of anti-platelet agents are currently available for clinical use: aspirin, the thienopyridines, and the intravenous GPIIb/IIIa antagonists. While these therapies are beneficial in the mean patient population, they may produce adverse effects in selected patient subgroups. In this article, we review the three main classes of antiplatelet drugs, discussing them in terms of the patient characteristics that are likely to influence their overall efficacy and safety.