During the last decade, an enormous amount of information has been gathered about the function of the platelet and its impact on percutaneous vascular interventions. With the discovery of the GP IIb/IIIa receptor, which is responsible for platelet aggregation, new drug antagonists have been developed to prevent platelet aggregation that may result in arterial thrombosis or platelet microembolization. These drugs include the three GP IIb/IIIa receptor antagonists approved by the Food and Drug Administration: abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat). These drugs have been used in several large studies to improve the outcome of coronary interventions and in conjunction with plasminogen activators to accelerate thrombolysis. In addition, because no oral GP IIb/IIIa inhibitor exists, other oral regimens have been developed with use of the thienopyridines, ticlopidine (Ticlid) and clopidogrel (Plavix), in combination with aspirin to prevent platelet aggregation and thrombosis. Because the majority of investigations have been performed in patients undergoing coronary interventions, knowledge of these data is necessary to attempt to translate the use of these antiplatelet drugs to peripheral vascular interventions. The goal of this article is to review the use of these agents in the percutaneous treatment of coronary artery disease and give insight to their potential utility in noncoronary interventions.