Thrombosis after the rupture of an atherosclerotic plaque often precipitates the acute coronary syndromes of unstable angina and myocardial infarction. The combination of aspirin and heparin has been shown to reduce the occurrence of both symptomatic and asymptomatic (“silent”) ischemia, myocardial infarction, and death in patients with these syndromes. However, heparin and aspirin each have significant limitations as antithrombotic drugs. Additionally, coagulation abnormalities may persist for several months after an acute ischemic event, and long-term anticoagulation may be beneficial. Because of the need for frequent anticoagulation monitoring and dosage adjustment, the use of heparin is limited to short-term treatment during the acute in-hospital phase. Recently several novel antithrombotic treatments have been developed. The benefits of direct thrombin inhibitors, platelet fibrinogen receptor antagonists, and low-molecular-weight heparins in the treatment of acute coronary syndromes have been demonstrated in randomized clinical trials. (Am Heart J 1998;135:S343-S352.)