The Thrombolysis in Myocardial Infarction (TIMI) trials are a series of studies begun in 1984, initially under the sponsorship of the National Heart Lung and Blood Institute and with data coordination in the first three trials expertly supplied by the Maryland Medical Research Institute. These trials have examined thrombolytic and antithrombotic regimens in acute myocardial infarction (MI) and unstable angina.(Table 1) The TIMI 1 trial compared the efficacy of intravenous streptokinase and tissue-type plasminogen activator (t-PA) in achieving coronary reperfusion. The TIMI 2 trial examined three strategies for acute MI, focusing on the role of adjunctive angioplasty following thrombolytic therapy, either immediately, at 18-48 hours after enrollment or as warranted clinically by the development of recurrent ischemia. The TIMI 3 trials explored the role of thrombolytic therapy and of an early invasive strategy in patients with the acute ischemic syndromes of unstable angina and non-Q wave MI. TIMI 4 compared three regimens of thrombolytic therapy, front-loaded t-PA, anistreplase and combination thrombolytic therapy. The TIMI 5 and 6 trials were pilot trials comparing the new thrombin inhibitor hirudin to heparin given in conjunction with aspirin and t-PA or streptokinase respectively. The TIMI 7 trial was a dose ranging trial of the related thrombin inhibitor hirulog in patients with unstable angina. The TIMI 8 trial, which was discontinued prematurely, was a double-blind trial comparing hirulog to heparin in patients with the acute ischemic syndromes of unstable angina and non-Q wave MI, and TIMI 9 is a double-blind trial comparing hirudin to heparin in conjunction with thrombolytic therapy and aspirin for acute myocardial infarction. The TIMI 10 trials will be as series of trials evaluating a more fibrin specific variant of t-PA, TNK-tPA. Together, these TIMI trials have both provided insights into the pathophysiology, and clinical course an provided information that is useful in the treatment of acute MI and unstable angina.