The combination of heparin and oral anticoagulants has been the treatment of choice for most patients with venous thromboembolism in the last two decades. Heparin has been proven to be effective when administered by intravenous continuous infusion or by subcutaneous injection. Oral anticoagulants should be started at the same time and heparin should be discontinued when the levels of the International Normalized Ratio reach the therapeutic range, between 2.0 and 3.0. Low molecular weight heparin has potential advantages over heparin and can be administered in subcutaneous weight-adjusted fixed doses without need for monitoring. This has made home treatment of a large proportion of patients possible. Randomized clinical trials have demonstrated the efficacy and safety of this approach. The optimal duration of the secondary prophylaxis with oral anticoagulants is still a matter of debate. The rate of recurrence has been shown to be elevated, particularly in those patients with idiopathic venous thromboembolism. The presence of an active cancer or a thrombophilic state may require long-term anticoagulation, although not all the congenital hypercoagulable states seem to carry the same level of risk. A 3-month therapy is recommended when a transient risk factor is identified; lifelong treatment is recommended for patients with a second episode of venous thromboembolism. In all other cases, 6 months are currently recommended, but thereafter close monitoring of the patients is advisable. The use of different treatment strategies such as vena caval filter placement, thrombolysis, and surgical thrombectomy should be restricted to a limited number of situations.