Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism, represents a significant source of morbidity and mortality. It is readily diagnosed with noninvasive modalities when there is a clinical suspicion. Most patients presenting with signs and symptoms of DVT have well-known risk factors, such as a history of VTE, malignancy, recent illness, or immobilization. A subset of individuals with idiopathic VTE have no readily identifiable risk factors. Therapeutic anticoagulation is the cornerstone of management in all patients with VTE. Adjunctive measures, such as thrombolysis and the use of vena cava filters, are indicated in select cases. The ideal duration of anticoagulation is unknown, but is often maintained long-term in patients with acquired or inherited thrombophilia. Warfarin is the only oral anticoagulant approved by the US Food and Drug Administration. Warfarin carries a substantial annual risk of bleeding complications, requires ongoing monitoring, and has extensive drug-drug interactions, which are causes for concern in patients requiring long-term anticoagulation. Alternative oral anticoagulants, such as direct thrombin inhibitors and factor Xa inhibitors, are subjects of active research in alternative agents for oral anticoagulation, and have been recently approved for prophylaxis in Canada and the European Union.