The role of glycoprotein (GP) IIb/IIIa-receptor inhibitors in managing ST-segment-elevation (STE) myocardial infarction (MI) is discussed. Strategies to improve outcomes in patients with STE MI have been directed toward rapidly establishing early reperfusion of the infarct-related artery and the downstream myocardial microvasculature and preventing reocclusion. Because of its superiority to fibrinolytic reperfusion, percutaneous coronary intervention (PCI) has emerged as the treatment of choice in patients with STE MI, including patients who are initially admitted to facilities not equipped to perform PCI. The combination of reduced doses of fibrinolytic agents with the GP IIb/IIIa-receptor inhibitors abciximab and eptifibatide has been explored as a means of improving reperfusion, both without PCI and as a means of facilitating PCI. Two large studies of the combination of abciximab and a reduced dose of a fibrinolytic agent in patients not undergoing PCI found a significant reduction in reinfarction, but mortality rates were unaffected and the risk of bleeding complications and thrombocytopenia was increased compared with the full dose of fibrinolytic agents alone. More encouraging results were seen with abciximab (with and without fibrinolytic therapy) in patients undergoing PCI. Pretreatment with eptifibatide (with and without concomitant fibrinolytic therapy) increased reperfusion prior to PCI, setting the stage for a large ongoing trial of eptifibatide in patients with STE MI undergoing PCI. This trial may help define the new standard of care for patients with STE MI, including the optimal use of GP IIb/IIIa-receptor inhibitors. Recent clinical trials in patients with STE MI show that the use of a GP IIb/IIIa-receptor inhibitor (with or without concomitant therapy with a reduced dose of a fibrinolytic agent) in conjunction with early PCI holds promise for achieving higher reperfusion rates and reducing the frequency of ischemic events.