Platelets have a newly appreciated and important role in many cancer-related processes, including tumor growth and metastases, angiogenesis, and promotion of a hypercoagulable state. Cancer patients commonly experience venous thromboembolism (VTE), a leading cause of mortality and a source of considerable morbidity and cost. The role of platelets in arterial thrombosis is well established, but emerging evidence supports the concept that platelets are also involved in initiation of VTE. This is particularly true in cancer-associated thrombosis as extensive new evidence shows that thrombocytosis and platelet activation are predictive biomarkers of VTE. The role of therapeutic anti-platelet agents has been proven effective at preventing VTE in non-cancer patients, and there are early data suggesting benefit in cancer patients as well. This review summarizes platelet-related predictive biomarkers of cancer-associated thrombosis, platelet-mediated mechanisms for VTE promotion in cancer patients, and anti-platelet agents in prevention of VTE.