The association of malignancies and venous thromboembolism (VTE) is a long held axiom in medicine. A growing number of studies have demonstrated that the risk of VTE associated with the hematological malignancies acute leukemia, lymphoma, and multiple myeloma is considerable. In fact, the incidence associated with these malignancies exceeds that for many solid tumors. Contributing factors include malignancy associated hypercoagulable factors; antineoplastic therapies such as high dose corticosteroids, L-asparaginase, and new immunomodulatory agents; central venous catheters; and hematopoietic growth factors. Primary and secondary pharmacological prophylaxis can be problematic in these patients who are often thrombocytopenic. Strategies to prevent VTE, especially upper extremity catheter-associated thrombosis need to be developed.