Drugs that inhibit factor Xa have been shown to reduce mortality and morbidity in acute coronary syndromes (ACS). Presently, factor Xa inhibition is most often achieved indirectly with the heparins and, increasingly, fondaparinux. Despite effective anticoagulation with indirect factor Xa inhibition there remains considerable mortality and morbidity in ACS. The recently developed direct factor Xa inhibitors (the xabans) appear to offer promise as alternatives to the heparins. We review the evidence behind indirect and direct factor Xa inhibition in non-ST-segment elevation ACS, ST-segment elevation myocardial infarction, and with percutaneous coronary intervention.