Because of the key role of thrombin in the pathogenesis of acute coronary syndrome (ACS), the appropriate selection of antithrombotic therapy is important. Unfractionated heparin (UFH) has been the agent of choice for decades. Unfortunately, UFH has a number of limitations related to its pharmacokinetic and pharmacodynamic properties. Low molecular weight heparins (LMWHs) are attractive alternatives to UFH for several reasons, including predictable anticoagulation and ease of administration. Two LMWHs (dalteparin and enoxaparin) have been approved as alternatives to UFH in patients presenting with unstable angina and non-ST-segment elevation myocardial infarction. Randomized, controlled trials, in addition to open-label series, indicate that LMWH can safely be the agent of choice with or without glycoprotein IIb/IIIa in the medical and upstream management of patients with ACS. Although the data are not definitive, several trials suggest that given intravenously, enoxaparin is safe as the sole antithrombotic agent in the catheterization laboratory.