Enoxaparin is a low-molecular-weight heparin (LMWH) derivative that exerts its anticoagulant activity through antithrombin III, an endogenous inhibitor of factor Xa and thrombin IIa. Unlike its unfractionated heparin (UFH) counterparts, enoxaparin has a greater bioavailability, lower incidence of heparin-induced thrombocytopenia and more stable and predictable anticoagulation, allowing fixed dosing without the need for monitoring. These advantages make it an attractive anticoagulant to be used in acute coronary syndrome management. Indeed, several clinical trials and meta-analyses have consistently demonstrated the efficacy of enoxaparin in reducing cardiovascular events and mortality in this population. Although initial clinical trials with enoxaparin during the early conservative approach suggested superior efficacy without differences in safety compared with UFH, emerging data in the current era of early revascularization approach indicate that superior effects of enoxaparin over heparin in reducing clinical events should be balanced against an increase in major hemorrhagic complications. Enoxaparin is a rational alternative to UFH in patients presenting with either unstable angina/non-ST-elevation myocardial infarction or ST-elevation myocardial infarction, with a clinically modest increase in bleeding complications.