Glycoprotein (GP) IIb/IIIa antagonists are a unique class of antiplatelet agents introduced for the management of patients undergoing percutaneous coronary intervention (PCI) and those presenting with unstable angina or non-ST segment elevation (NSTE) myocardial infarction (MI), collectively recognized as acute coronary syndromes (ACS). Eptifibatide, abciximab, and tirofiban HCl are three GPIIb/IIIa antagonists approved for use by the Food and Drug Administration. Of the three agents, eptifibatide is approved for use in both PCI and NSTE ACS patient populations, whereas abciximab is indicated for patients undergoing PCI, and tirofiban is approved for patients with NSTE ACS. Dose selection for the initial trials using the three parenteral antagonists was based on in vitro and ex vivo pharmacodynamic assays conducted under different blood collection and platelet function assay conditions. Recent comparative pharmacodynamics studies, which used newly defined and standardized assay conditions, indicate that the platelet aggregation inhibition achieved with these dosing regimens is variable. Therefore, the differences in clinical efficacy as evidenced in the more recent clinical studies (e.g., Enhanced Suppression of the Platelet Receptor GPIIb/IIIa using Integrilin Therapy [ESPRIT], Global Use of Strategies to Open Occluded Coronary Arteries IV Acute Coronary Syndromes [GUSTO-IV ACS], and Do Tirofiban HCl and ReoPro Give Similar Efficacy Outcomes Trial [TARGET]) may be related to the variable antiplatelet effects of the approved dose regimens.