Venous thromboembolic disease (VTE) is a common complication of malignancies affecting the central nervous system (CNS), both in the perioperative period and throughout the disease course. Until recently, the perceived risk of intracranial hemorrhage in patients with CNS malignancies was felt to be a relative contraindication to systemic anticoagulation, and most patients were managed with nonpharmacologic methods in both the prophylactic and treatment setting. However, several studies of the safety and efficacy of anticoagulation in both neurosurgical and cancer patients have challenged the previous dogma, and routine use of unfractionated heparin or low molecular weight heparin (LMWH) for VTE prophylaxis in patients undergoing craniotomy for CNS malignancy is recommended. Likewise, treatment of established VTE in this population with heparins is recommended, at least initially, followed by long-term treatment either with heparin or oral warfarin. Complications of inferior vena cava (IVC) filters, used as an alternative to systemic anticoagulation, appear to be more common in brain tumor patients with VTE, lending further support to treatment with systemic anticoagulation when possible. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, LMWH is recommended in brain tumor patients with newly diagnosed VTE, followed by long-term warfarin or LMWH.