As the number of anticoagulant drugs increases and new ones are brought to market, the utility of the routine screening coagulation tests of today—namely the prothrombin time and activated partial thromboplastin time—will be significantly reduced in many clinical situations. Although the new anticoagulants are designed to require less frequent monitoring, it is imperative that the proper test is selected in situations where monitoring is needed. In addition, tests that are designed for the new generation of drugs may be informative in certain situations for monitoring the anticoagulants that have been in use for many years. Here, we present the chromogenic antifactor Xa assay and demonstrate its utility and its limitations in monitoring three anticoagulant drugs (unfractionated heparin, low molecular weight heparin, and fondaparinux) as well as one emerging anticoagulant, rivaroxaban. Am. J. Hematol. 2011. © 2011 Wiley-Liss, Inc.