Heparins and VKAs have been the cornerstones of anticoagulation therapy for several decades and these agents have become most important drugs in the primary and secondary prevention of venous and arterial thromboembolic disease. Although effective, their use has been hampered by numerous limitations. In the search for new agents matching the 'ideal' anticoagulant profile, a number of different steps in the coagulation cascade have been targeted, including direct thrombin inhibition, and direct inhibition of Factor Xa. There are currently a host of promising new agents at various stages of development and clinical evaluation. With potential benefits including predictable efficacy, rapid onset of action, ability to bind clot-bound coagulation factors and no requirement for therapeutic monitoring, these new agents are set to improve the management of thromboembolic disorders.