Patients with multiple myeloma (MM) are at an increased risk of venous and arterial thrombosis. The pathogenesis remains unclear, but probably involves several factors such as activation of procoagulant factors, acquired activated protein C resistance, and inflammation. In addition to general risk factors for venous thromboembolism, such as older age, immobility, surgery, and inherited thrombophilia, there are some MM-specific and treatment-related factors that contribute to the increased risk. The risk for venous thromboembolism is high when patients are treated with thalidomide or lenalidomide in combination with dexamethasone or multi-agent chemotherapy. Thromboprophylaxis should be given in these settings. Which agent is the most appropriate is a matter of debate, but aspirin, low-molecular-weight heparin, and warfarin all seem to be effective. This review discusses risk factors for thromboembolism in MM and general, disease-specific and treatment-related mechanisms for thrombosis. Recommendations for thromboprophylaxis are described and treatment choices for venous thrombosis in MM patients are reviewed.