The circulating platelet and the soluble coagulation protein thrombin play key roles in the thrombosis responsible for the acute coronary syndromes. The standard antiplatelet and antithrombin agents used today in patients with acute coronary syndromes are aspirin and heparin. Despite our experience with these agents, they both have significant limitations. A number of new antiplatelet drugs, including clopidogrel and the glycoprotein IIb/IIIa antagonists, have been investigated in recent large clinical trials and show significant promise both in patients undergoing angioplasty and those with acute coronary syndromes. The results of recent trials with new antithrombin agents have been less impressive. Low-molecular-weight heparins appear to be beneficial in patients with acute coronary syndromes. Recent trials with direct thrombin inhibitors in patients with acute coronary syndromes have demonstrated modest benefit, but also revealed their narrow therapeutic window and associated risk of bleeding. Further trials with novel antiplatelet and antithrombin agents in patients with acute coronary syndromes are ongoing.