Cancer and its treatments are well-recognized risk factors for venous thrombo-embolism (VTE). Although solid tumors have historically been associated with VTE, more recent data suggest similar risk in patients with hematologic malignancies as well. The risk of VTE is not equal for all cancer patients or even in the same patient over time. In addition to well-known risk factors such as tumor site, stage, chemotherapy and comorbidities, candidate biomarkers have recently been identified including platelet and leukocyte counts, tissue factor and P-selectin. A validated risk model incorporating some of these risk factors and biomarkers has been shown to be predictive of VTE in cancer. VTE is associated with mortality, morbidity, potential delay in treatments for cancer and consumption of scarce health-care resources. Hence, reducing VTE with targeted prophylaxis could improve outcomes for cancer patients.