The recently established correlation between bleeding events and clinical outcomes in patients with coronary artery disease undergoing either non-invasive or invasive treatment for acute coronary syndromes (ACS) highlights the unmet need for safer anticoagulants that can be used in conjunction with dual or triple antiplatelet therapy. The central position of the coagulation factors IIa and Xa within the coagulation system account for their prominent role as targets for anticoagulants. Unfractionated heparin (UFH) achieves a variable indirect inhibition of both factors. The low molecular weight heparins (LMWH) show favourable pharmacokinetics over UFH and have a more pronounced activity against factor Xa as opposed to thrombin which may partially account for the benefits observed with LMWH in clinical trials. New agents that have been developed allow for a selective inhibition of factor Xa. Recently, exciting results have been reported with an indirect selective inhibitor of factor Xa in patients with ST-elevation myocardial infarction (STEMI) -acute coronary syndromes (ACS) and non-STEMI-ACS. In this article the pharmacology of the indirect selective factor Xa inhibitors Fondaparinux and Idraparinux will be discussed along with the direct selective factor Xa inhibitors DX-9065a and Otamixaban in the setting of interventional cardiology.