Factor Xa is a serine protease that has a critical role in the blood coagulation cascade by ultimately regulating the production of thrombin. There is now ample evidence for the role of Factor Xa inhibitors as anticoagulants and they represent potential new therapeutic agents for the treatment and prevention of arterial and venous thrombosis. During the past five years, research in the field of Factor Xa inhibitors has been marked with enormous efforts to identify highly potent, selective and orally-active agents. This research has led to the discovery of a number of clinical candidates that are currently progressing at different stages of drug development. This review examines the patent and scientific literature during the period 2000 – 2005.