Thrombosis is a common complication of malignancy. This is felt to be related to increased activity of the coagulation system as evidenced by markers of accelerated thrombin generation and increased platelet reactivity. Alterations in the hemostatic balance have been documented in patients with malignancy with increased tissue factor (TF) generation and the production of a cysteine protease. These can stimulate the coagulation mechanism via the extrinsic pathway and/or by activating factor X. The thrombotic presentations in malignancy are protean and may be venous or arterial. The underlying clinical pictures may be related to varying degrees of consumptive coagulopathy, microangiopathy, and nonbacterial endocarditis. Prophylaxis and management are, to a significant degree, dependent on the underlying malignancy and the prothrombotic mechanism. Specific agents and drugs must be selected from an expanding menu of options that includes unfractionated heparin, low-molecular-weight heparin (LMWH), warfarin, plasma apheresis, and the newer antithrombin agents.