Despite major advances made over the last decade, mortality following acute myocardial infarction (MI) is still high even for patients treated with the "front-loaded" recombinant tissue-type plasminogen activator (rt-PA) regimen: 30-day mortality is 6.3%, and it is associated with fatal cerebral hemorrhage in 1.5%. Further improvement of short- and long-term prognosis can be achieved if infusion of the thrombolytic agent starts early, if reperfusion occurs more rapidly, and if a persistent thrombolysis in myocardial infarction (TIMI) grade 3 flow of the infarct-related artery can be achieved. These prerequisites for optimal preservation of ventricular function and predictors of a favorable outcome. New treatment strategies, e.g., more accelerated dosage regimens of established thrombolytic agents, new combination therapies, and new thrombolytic agents, with or without addition of more specific and more potent new antithrombotic agents, may further improve the efficacy of thrombolysis in acute MI during the late 1990s.