Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in patients with cancer. The risk of VTE varies over the natural history of cancer, with the highest risk occurring during hospitalization and after disease recurrence. Patient and disease characteristics are associated with further increased risk of VTE in this setting. Specific factors include cancer type (eg, pancreatic cancer, brain cancer, lymphoma) and the presence of metastatic disease at the time of diagnosis. VTE is a significant predictor of increased mortality during the first year among all types and stages of cancer, with metastatic disease reported to be the strongest predictor of mortality. VTE is also associated with early death in ambulatory patients with cancer. These data highlight the need for close monitoring, prompt treatment, and appropriate preventive strategies for VTE in patients with cancer. The American Society of Clinical Oncology and the National Comprehensive Cancer Network have issued guidelines regarding the prophylaxis and treatment of patients with cancer. This review summarizes the impact of VTE on patients with cancer, the effects of VTE on clinical outcomes, the importance of thromboprophylaxis in this population, relevant ongoing clinical trials examining the prevention of VTE, and new pharmacologic treatment options. Cancer 2011. © 2010 American Cancer Society.