Compounds which inhibit the coagulation cascade and antagonize platelet function are fundamental to the successful treatment of acute coronary syndromes. In a high proportion of patients with acute myocardial infarction, unstable angina, or sudden cardiac death, the acute ischaemic event is precipitated by intracoronary thrombus. Occlusive or non-occlusive thrombi have been found in the majority of cases, either in vivo or at autopsy. Aspirin and unfractionated heparin have been the cornerstones of antithrombotic therapy in such patients for the past decade, but while their benefits have been convincingly demonstrated, there are significant pharmacokinetic, pharmacodynamic, and clinical limitations. These limitations have provided the impetus for the development of newer antithrombotic agents with several theoretical advantages over aspirin and heparin. This paper has four aims. First it reviews the pathogenesis of intracoronary thrombi in acute coronary artery syndromes. Second, it outlines the limitations of current antithrombotic therapies. Third, it explores the potential advantages of new antithrombin and antiplatelet compounds, which may be understood and classified by their mechanism of action (Table 1); how the theoretical advantages may translate into clinical practice will be examined. Fourth, the initial clinical experience with these new agents will be reviewed briefly.