Complete thrombolytic occlusion of a coronary artery has been thought to be the etiology of a acute myocardial infarction (MI) since 1912 and was proven by coronary angiography in 1980. Dissolution of the thrombus with the use of pharmacological agents has been proposed to decrease the morbidity and mortality associated with acute MI. This article reviews the historical development, pharmacology, efficacy, and complications associated with the four currently available thrombolytic agents. In 1912, James Herrick proposed that acute myocardial infarction (MI) was due to thrombotic occlusion of the coronary artery and was not inevitably associated with a fatal outcome. Although this view was revolutionary, it was virtually ignored for some 50 years. During the interim, the prevailing concept of the pathogenesis of acute MI revolved around gradual occlusion of a coronary artery by an atherosclerotic process with secondary thrombotic occlusion. Marcus DeWood settled the debate regarding the pathogenesis of acute MI in 1980 with a landmark publication which documented angiographically the presence of an intracoronary thrombus in patients with acute transmural myocardial infarction. He found that 87% of the patients who underwent cardiac catheterization within four hours of the onset of chest pain had thrombotic occlusion of the infarct-related artery. This percentage decreased to approximately 65% when the cardiac catheterization was performed within 12-24 hours after the onset of symptoms. Herrick's hypothesis, plus documentation that coronary thrombosis resulted in an acute MI presented investigators with the theory that thrombolytic agents could potentially prevent or limit the extent of myocardial damage. This discussion will focus on the historical development, pharmacology, and current knowledge regarding the efficacy of the available thrombolytic agents in the United States.