Current evidence suggests a central role for antithrombotic agents such as unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in the management of acute coronary syndromes (ACS). In patients with acute myocardial infarction, several studies have shown that LMWHs may represent an effective alternative to UFH as an adjunct to thrombolytic therapy and are not associated with an increased risk of major bleeding. In patients with unstable angina or non-ST-segment elevation myocardial infarction, trials have shown that the LMWH enoxaparin significantly reduces the risk of cardiovascular events, compared with UFH, while other trials have shown that the combination of enoxaparin and a glycoprotein IIb/IIIa antagonist is not associated with an excess risk of bleeding. However, LMWHs are significantly more expensive that UFH. Recently, newer antithrombotic agents such as fondaparinux and bivalirudin have shown equivalent efficacy to the heparins with less bleeding and appear clinically attractive. This review examines the current evidence for the efficacy and safety of antithrombotic agents in ACS.