Timely initiation of thrombolytic therapy can achieve coronary reperfusion, a reduction in infarct size, a preservation of left ventricular function and a reduction in mortality. It is therefore an established procedure in acute myocardial infarction. The major drawback is an increased rate of bleeding. As a consequence thrombolytic therapy is at present withheld from many patients with contraindications. Other problems include relative inefficacy of presently available thrombolytic agents and early reocclusion of primarily successfully reperfused vessels. New approaches to optimize the risk/benefit ratio for the patient and to make thrombolytic therapy available to more patients include new antithrombin and antiplatelet agents as adjunctive therapy, synergistic combinations of plasminogen activators, mutants of t-PA and prourokinase, chimeric molecules and antibody-targeted thrombolysis.