In the setting of acute myocardial infarction, thrombolytic therapy fails to restore an adequate epicardial flow in a large number of patients. Although an increasing number of patients undergoes a percutaneous coronary intervention (PCI) after failed thrombolysis, this treatment has been poorly investigated. This review focuses particularly on the safety and prognostic impact of glycoprotein (GP) IIb/IIIa receptor inhibitors after failed thrombolysis. GPIIb/IIIa inhibitors have been demonstrated to improve the clinical outcome in patients undergoing primary PCI. However, the increased risk of bleeding with the administration of potent antiplatelet drugs after full-dose thrombolytics has limited the widespread use of GPIIb/IIIa inhibitors during rescue PCI. We recently reported that abciximab treatment during rescue PCI has a beneficial effect on the short-term prognosis, without excess bleeding complications. This result can be achieved by using the radial approach, a low-dose weight-adjusted heparin regimen, and by limiting the use of aortic counterpulsation. In conclusion, in case of thrombolysis failure, patients should be referred to tertiary hospitals where rescue PCI can be performed with expertise.