The diagnosis of venous thromboembolic disease, and pulmonary embolism in particular, remains problematic. Physicians should strongly consider empiric anticoagulation if the best available diagnostic tests are inconclusive, because treatment is usually safe and successful. Twice-daily subcutaneous low-molecular-weight heparin, dosed without monitoring, may eventually replace standard heparin for most treatment of venous thromboembolism, but it is not yet labeled for the treatment of pulmonary embolism. Deep venous thromboembolism and pulmonary embolism should be treated with anticoagulants rather than inferior vena cava filters, even in oncology patients, unless anticoagulation is contraindicated; if so, when the contraindication remits, anticoagulation should be employed. The most effective prophylaxis of venous thromboembolism in at-risk patients should be used, with prolonged duration if evidence from clinical trials supports efficacy and safety. Low-dose warfarin should be used to prevent venous thrombosis and indwelling central venous catheter thrombosis in patients with cancer.