Warfarin and related compounds are efficacious and safe in a variety of clinical thrombotic disorders; however, these drugs have a narrow therapeutic window, whereby inadequate therapy is associated with an increased thrombotic risk and overanticoagulation is associated with bleeding. Therefore, attempts have been made to develop alternatives to warfarin. Ximelagatran, an oral direct thrombin inhibitor, has been shown to be as efficacious and safe as warfarin for the prevention and treatment of different thrombotic disorders. This article reviews the pharmacology of the coumarins, the most commonly used vitamin K antagonists, and the practical aspects regarding their use in the management of thrombotic disorders. The future role of the oral direct thrombin inhibitor ximelagatran also is reviewed.