Reperfusion with a regimen of fibrinolytic therapy, aspirin, and unfractionated heparin is limited by a less than desirable reperfusion rate, an excessive reocclusion rate, a dose-limiting intracranial hemorrhage rate, and a competitive posture relative to direct coronary angioplasty. Only 50% to 60% of patients achieve early Thrombolysis in Myocardial Infarction grade 3 flow within 90 minutes with the most effective thrombolytic regimens. Even after initial reperfusion is achieved, transient and permanent reocclusion occurs too often and is associated with a high mortality rate. As more older patients are being treated, intracranial hemorrhage is becoming more common. Finally, the risk of bleeding and procedural failure has been high in patients who received an acute percutaneous interventional procedure shortly after treatment with fibrinolytic therapy. Early studies combining full-dose fibrinolytic treatment and glycoprotein IIb/IIIa inhibitors have been promising with regard to overcoming these limitations, but concern about bleeding has hindered this strategy. Several recent trials have evaluated full-dose abciximab with reduced-dose fibrinolytic therapy and have yielded promising results. The complementary nature of the results from different trials is striking, with substantial evidence that approximately half the conventional dose of fibrinolytic therapy combined with full-dose glycoprotein IIb/IIIa inhibition with abciximab achieves high rates of grade 3 flow and excellent clinical outcomes. This approach will now be tested in a large-scale mortality trial.