Thromboembolic disorders are major causes of morbidity and mortality. It is well-recognised that the pathogenesis is different for arterial and venous thrombosis; however, both involve coagulation activation. Anticoagulants are used for the prevention and treatment of a wide variety of thromboembolic and related conditions. Agents with anti-inflammatory properties in addition to anticoagulation may be particularly beneficial. Traditional anticoagulants, although effective, are associated with certain limitations. Understanding the pathological processes associated with thrombosis and the rational target for anticoagulation is essential, not only for the development of safer and more effective agents, but also for better clinical management of patients who require anticoagulation therapy. In recent years, new oral agents that target single enzymes of the coagulation cascade have been developed – some of those are in advanced stages of clinical development. Based on scientific rationale, both factor Xa and thrombin are viable targets for effective anticoagulation.