For the treatment of acute myocardial infarction, heparin has been a topic of continuing debate for the past four decades. After review of the available data, the American College of Cardiology/American Heart Association Guidelines for the Early Management of Patients with Acute Myocardial Infarction, published in 1990, recommended intravenous heparin administration together or immediately after thrombolytic therapy to maintain the activated partial thromboplastin time approximately 1.5 to 2.0 times the control value for 24 to 72 hours. Over the past five years, with the proven benefits or thrombolytic therapy and antiplatelet therapy, investigators have been in search of the ideal thrombolytic agent as well as the best adjunctive antithrombotic strategy. We review a number of angiographic patency trials as well as the major thrombolytic mortality reduction trials in which adjunctive heparin therapy was directly assessed. These trials established the need for intravenous heparin administration with tissue plasminogen activator, but, on the other hand, do not substantiate the need for either subcutaneous or intravenous heparin use with streptokinase. New data from a large scale trial emphasizes the importance of maintaining the aPTT in the 55-70 second range to prevent bleeding complications and optimize clinical outcomes.