Over the last two decades, converging observations on the close interactions between platelets and the coagulation system, and on the biology of the vessel wall, atherosclerosis, and inflammation, have established the role of intravascular thrombus formation as the immediate trigger for acute coronary syndromes. This progress in the understanding of the pathophysiological processes has been matched by the incremental success of treatment achieved by the introduction of aspirin and heparin, new antiplatelet agents (adenosine diphosphate [ADP] and GP IIb/IIIa [GP, glycoprotein] receptor antagonists), and new anticoagulants (low-molecular-weight heparins and direct thrombin inhibitors), and the judicious use of combined antiplatelet therapy and combined antiplatelet and anticoagulant therapy. This article reviews the mechanisms of thrombus formation, the current antithrombotic therapy, and the new antithrombotic therapy that is emerging at an accelerated pace, and the rationale for their use...