Glycoprotein (GP) IIb/IIIa receptor antagonists inhibit the binding of ligands to activated platelet GP IIb/IIIa receptors and, therefore, prevent the formation of platelet thrombi. They have been extensively studied in patients undergoing percutaneous coronary intervention (PCI). Eptifibatide, one of the approved GP IIb/IIIa inhibitors, is a small heptapeptide that is highly selective and rapidly dissociates from its receptor after cessation of therapy. In clinical studies, concomitant administration of eptifibatide in patients undergoing elective PCI reduced thrombotic complications in the IMPACT-II (Integrilin to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II) and ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy) trials. In the PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) trial, which included 10,948 patients with non-ST-elevation acute coronary syndromes, eptifibatide significantly reduced the primary end point of death and non-fatal myocardial infarction at 30 days compared with placebo. In patients with ST-segment elevation myocardial infarction (STEMI), eptifibatide has been studied as adjunct to primary PCI and improved epicardial flow and tissue reperfusion. Studies are now evaluating eptifibatide in high-risk patients with non-ST elevation acute coronary syndromes (NSTE-ACS) and a planned early invasive strategy in the EARLY-ACS (Eptifibatide Administration prior to Diagnostic Catherization and Revascularization to Limit Myocardial Necrosis in Acute Coronary Syndrome) trial and in patients with primary PCI for STEMI in comparison to abciximab in the EVA-AMI (Eptifibatide versus Abciximab in Primary PCI for Acute Myocardial Infarction) trial. After the completion of these trials, the value of etifibatide in patients undergoing PCI in different indications can be determined.