The combination of unfractionated heparin or low molecular weight heparin and oral anticoagulants is currently the treatment of choice for most patients with venous thromboembolism. Oral anticoagulants are started at the same time and heparin is discontinued after at least 5 days 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 is administered in subcutaneous weight-adjusted fixed doses without need for monitoring. This has made the home treatment of a large proportion of patients possible. Randomized clinical trials and several subsequent reports from clinical practice have demonstrated the efficacy and safety of this approach. The results of currently ongoing trials aimed to assess the efficacy and safety of newer compounds for the initial treatment of venous thromboembolism are expected. Oral direct thrombin inhibitors or selective factor-Xa inhibitors have the potential to become the treatment of choice in the next decade. 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 patients with idiopathic venous thromboembolism. A 3-month therapy is therefore currently recommended when a transient risk factor is identified, life-long treatment is recommended for patients with a second episode of venous thromboembolism. The presence of 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. In all other cases, 6 months are recommended, but a long-term monitoring of the patients is advisable. The use of more aggressive strategies such as thrombolysis is limited to patients presenting with massive pulmonary embolism or signs of right ventricular dysfunction.