Deep vein thrombosis (DVT) and pulmonary embolism (PE) are both part of one entity: venous thromboembolic disease (VTE). Patients with DVT should be treated acutely with low molecular weight heparin (LMWH) or adjusted-dose unfractionated heparin (UFH). Patients with PE should be treated with intravenous UFH. LMWH may be used only in patients with non-massive PE. When UFH is used, the dose should be sufficient to prolong the aPTT to a range between 1.5 to 2.0 control. In comparison to UFH, LMWH offers the major benefits of convenient dosing and facilitation of outpatient treatment. LMWH treatment may offer a survival benefit in patients with cancer. Treatment with UFH or LMWH should be continued for at least 5 days. Oral anticoagulant treatment can be initiated during the first 3 days with an overlap with heparin for at least 4 to 5 days. For most patients, treatment with warfarin can be started together with heparin. Heparin can be discontinued when the INR has been therapeutic (range 2.0 to 3.0) for 2 consecutive days. For massive PE or severe ileofemoral thrombosis, a longer period of heparin therapy (approximately 10 days) is recommended. Oral anticoagulant therapy should be continued for at least 3 months in patients with a first episode of VTE if they have a reversible or time-limited risk factor and for at least 6 months is they have idiopathic VTE. For patients with recurrent idiopathic VTE or continuing risk factor such as cancer, treatment for 12 months or longer is recommended. The use of thrombolytic agents in the treatment of VTE continues to be highly individualized. In general, patients with hemodynamically unstable PE or massive ileofemoral thrombosis, who are at low risk to bleed, are the most appropriate candidates. Thrombolytic therapy is indicated in patients with massive PE, as shown by shock or hypotension. Most contraindications for thrombolytic therapy in massive PE are relative. The use of thrombolytic therapy in patients with sub-massive PE (right ventricular hypokinesia) is controversial. Thrombolysis is not indicated in patients without right ventricular overload. New antithrombotic agents such as direct thrombin inhibitors or synthetic factor Xa inhibitors provide promising results in clinical trials.