Thromboembolism affects many patients with solid tumors and clonal hematologic malignancies. Thromboprophylaxis with low-molecular-weight heparin (LMWH) is indicated for surgery and other high-risk situations, but not routinely for central venous catheters or nonsurgical, ambulatory management. Thrombotic events require full anticoagulation for the duration of active disease and/or the prothrombotic stimulus. LMWHs are safe and more effective than both unfractionated heparin for initial therapy and warfarin for secondary prevention. Anti-inflammatory and antiangiogenic properties might account for this advantage and for a survival benefit of chronic LMWH in subgroups of cancer patients. Ongoing studies are characterizing the cost-effectiveness and antitumor mechanisms of LMWHs, the potential utility of newer anticoagulants, and the ability of predictive models to identify high-risk candidates for thromboprophylaxis.