Intravenous fibrinolytic therapy is used widely in the treatment of ST-elevation acute myocardial infarction. Advances in this therapeutic modality during the past 5 years include new third-generation fibrinolytic agents and creative strategies to enhance administration and efficacy of fibrinolytic therapy. Several of the new agents allow for single- or double-bolus injection. A number of ongoing large randomized trials are attempting to determine whether the combination of fibrinolytic therapy with low-molecular-weight heparin or a glycoprotein IIb/IIIa antagonist enhances coronary reperfusion and reduces mortality and late reocclusion. One large prospective trial is investigating the potential benefit of prehospital administration of fibrinolytic therapy. This article summarizes recent safety and efficacy data on fibrinolytic therapy, with particular emphasis on the new third-generation fibrin-specific agents; reviews the preliminary data on facilitated fibrinolysis; and discusses the rationale for prehospital administration of fibrinolytic therapy.