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Warfarin is the only orally administered anticoagulant drug in major use in the United States. Numerous clinical trials have demonstrated its efficacy in the prevention and treatment of venous thromboembolic disease, as well as in the prevention of systemic embolization due to atrial fibrillation and other cardiac conditions. Patients administered warfarin require specialized dosing and monitoring to individualize therapy, maximize efficacy, and decrease the incidence of associated hemorrhagic and thromboembolic complications. Monitoring requires knowledge of the influence of drug and food interactions, disease, and other patient factors on response to warfarin. This article reviews current concepts of the varying role of warfarin in long-term anticoagulation, with a special focus placed on dosing and monitoring techniques necessary to achieve desired therapeutic outcomes in the ambulatory patient.