Platelet-mediated thrombosis has been recognized as the primary pathophysiologic mechanism of acute coronary syndromes (ACS) and acute complications of percutaneous coronary intervention (PCI). Despite the clinical efficacy of the two most widely used antithrombotic agents, aspirin and heparin, each of them has significant therapeutic limitations. As a result, thrombosis and clinical events may occur despite the use of aspirin and heparin. The discovery that the platelet glycoprotein (GP) IIb-IIIa represents the final common pathway to platelet aggregation and the growing recognition of the key role of platelets in the progression of thrombosis prompted the development of several GP IIb-IIIa inhibitors as a potentially more effective form of antithrombotic therapy. Numerous trials of various GP IIb-IIIa inhibitors as adjuncts to PCI have strongly supported this hypothesis. The subject of this supplement is the review of more recent evaluations of GP IIb-IIIa inhibitors in the context of various treatment strategies for the management of patients with unstable angina or non-ST-segment elevation myocardial infarction, collectively known as non-ST-segment elevation ACS. Appropriate translation of these trials into clinical practice requires not only the knowledge of the trials' results but also the understanding of the design of individual studies, most notably the entry criteria and patient management strategies.