Venous thromboembolism (VTE), which includes deep venous thrombosis and pulmonary embolism, is a major public health problem associated with increased morbidity and mortality. Despite the high recurrence risk associated with unprovoked VTE, extended anticoagulation remains controversial. Oral antithrombotic agents for extended VTE treatment comprise the vitamin K antagonists, aspirin, and the direct oral anticoagulants (also known as target-specific oral anticoagulants and formerly known as the new or novel oral anticoagulants) including rivaroxaban, dabigatran, apixaban, and edoxaban. The efficacy of these anticoagulants in reducing the risk of VTE recurrence (>80%-90% relative risk reduction) is offset by the risk of major bleeding that approaches 3% per year. Stratifying risks of recurrence and bleeding to identify patients at low, intermediate, or high risk and carefully considering the pharmacologic profile of the antithrombotic agents will help clinicians in choosing the optimal anticoagulant and duration and/or surveillance strategy. This review will discuss the current guidelines for extended VTE treatment, review the clinical trials involving the direct oral anticoagulants, and present the clinical considerations and concerns involving extended therapy.