During the past decade, the general acceptance of the primary role of thrombosis in acute myocardial infarction (AMI) has led to intense interest in the potential efficacy of reperfusion therapy, particularly thrombolytic therapy, in AMI. Accumulating evidence indicates that systemic thrombolytic therapy administered early after the onset of symptoms of AMI can restore infarct-related artery patency, salvage myocardium, and reduce mortality. Recommendations about the proper use of thrombolytic therapy, contraindications, and concomitant therapies (such as aspirin, heparin, nitrates, beta-adrenergic blocking agents, and calcium channel blockers) are reviewed. Although percutaneous transluminal coronary angioplasty (PTCA) is useful for subsets of patients with AMI (for example, patients with anterior infarctions with persistent occlusion of the infarct-related artery after thrombolytic therapy and those with cardiogenic shock), a conservative strategy, including angiography and PTCA only for postinfarction ischemia, is indicated for most patients with AMI in whom initial thrombolytic therapy is apparently successful. The use of PTCA after failed thrombolysis or as direct therapy for AMI seems promising, although further comparisons of PTCA and intravenous thrombolytic therapy are needed. Ongoing studies should help further define the risk-to-benefit ratio of various reperfusion strategies in different subsets of patients, define time limitations for reperfusion therapy, and provide data on therapeutic modalities that will limit reperfusion injury and therefore enhance salvage of myocardium.