Cancer patients are clearly at increased risk for venous thromboembolism (VTE). However, the risk is not equal for all cancer patients or even in the same patient over the course of the natural history of cancer. VTE prophylaxis has been shown to be beneficial in certain high-risk populations such as post-surgical or hospitalized cancer patients but data in the ambulatory setting are conflicting. A majority of solid tumor patients are currently treated in the ambulatory setting and studying risk factors for VTE and their interaction is essential to identifying a population of ambulatory cancer patients that could benefit from prophylaxis. In this review, we evaluate the literature on risk factors for cancer-associated VTE and discuss data from a large observational study of cancer patients receiving chemotherapy which has revealed novel risk factors for chemotherapy-associated VTE. Finally, we discuss model-based approaches to risk-stratifying cancer patients that incorporate the known multiple risk factors for VTE and can help identify high-risk subgroups in the cancer population.