Thrombolytic therapy has become standard care in treating acute myocardial infarction. Fibrinolytic drugs such as streptokinase, APSAC and urokinase are non fibrin specific, and induce systemic activation of the fibrinolytic process, while t-PA and prourokinase are fibrin specific since they are able to activate mainly fibrin bound plasminogen. Both groups of thrombolytics exert different and opposing effects on the hemostatic balance: indeed, they have antithrombotic as well as prothrombotic properties, and this may be important for explaining therapeutic failures or reocclusions. New strategies have been considered or are under investigation for further improving the already excellent efficacy of thrombolytic treatment in myocardial infarction: combined administration of fibrinolytic agents, thrombus-targeted thrombolytic drugs, association with other drugs both effective and ineffective on the hemostatic process. At present, however, the first priority still seems to be a continuing effort to increase the percentage of patients treated with thrombolytics, since the benefits of this therapy have already been clearly demonstrated.