Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke. In patients with suspected VTE, the diagnosis can be readily established with noninvasive testing: compression ultrasonography for the diagnosis of DVT and computed tomographic pulmonary angiography for the diagnosis of pulmonary embolism. Many patients with VTE have well-known risk factors such as a personal or family history of VTE, recent surgery, or hospitalization for medical illness or cancer. However, up to half have no readily identifiable risk factors and are said to have unprovoked VTE. Anticoagulation therapy is the mainstay for treatment of VTE. Adjunctive measures such as thrombectomy, thrombolytic therapy, or inferior vena cava filters are reserved for selected patients. The duration of anticoagulant therapy varies depending on whether the VTE is provoked or unprovoked and whether the provoking factors are transient or persistent. Direct oral anticoagulants, such as apixaban, dabigatran, edoxaban, and rivaroxaban, have essentially replaced warfarin for the treatment of VTE and are increasingly being used in place of low-molecular-weight heparin for the treatment of VTE in selected cancer patients.