Glycoprotein (GP) IIb/IIIa inhibitors have been extensively studied in the setting of percutaneous coronary intervention (PCI) and in the management of non-ST-segment elevation acute coronary syndromes. However, the use of GP IIb/IIIa inhibitors is less well established in the setting of acute ST-segment elevation myocardial infarction (MI). Multiple nonrandomized studies suggest that combination therapy with GP IIb/IIIa inhibitors and thrombolytic agents leads to increased rates of TIMI 3 flow. However, two clinical trials involving over 22,000 patients demonstrated that combination therapy is associated with only modest reductions in major adverse cardiac events, does not reduce mortality, and is associated with an increase in bleeding. In the setting of primary PCI, four clinical trials involving over 3,000 patients demonstrated that GP IIb/IIIa inhibition results in a significant decrease in the need for urgent target vessel revascularization but not in reductions of death or recurrent MI. Thus, GP IIb/IIIa inhibition may provide only limited benefits in the setting of acute ST-segment elevation MI.