Although traditional anticoagulant regimens are highly effective and safe in most patients with venous thromboembolism (VTE), the aggressive natural history of VTE and the high risk of serious bleeding in cancer patients can complicate the management of VTE. In addition, because few clinical trials have focused on the prevention and treatment of VTE in this unique patient population, many clinical questions regarding the care of cancer patients with VTE remain unanswered. Currently, low-molecular-weight heparins and oral vitamin K antagonists are the most commonly used agents for the primary and secondary prophylaxis of VTE in patients with or without cancer, but their use is associated with pharmacological and practical limitations. This review will provide an up-to-date summary of the clinical trials that have addressed the management of VTE in patients with cancer. A brief discussion of the potential application of novel anticoagulants in these clinical settings is also included.