Glioblastoma Multiforme (GBM) is a uniformly fatal disease with a median survival of approximately 15 months. Recent monoclonal antibody therapies such as Bevacizumab (Avastin) have been shown to be active in GBM and to prolong survival in patients with recurrent malignant glioma. Therefore, patients routinely receive intravenous (i.v.) Bevacizumab (10 mg/kg) every two weeks when they have recurred following standard therapy with chemoradiation. I.v Bevacizumab; however, can cause significant systemic side effects including bowel perforation and pulmonary embolism. In addition, the blood brain barrier (BBB) continues to provide an obstacle to the effective delivery of the antibody to the brain tumor bed. In order to overcome the BBB, and to limit the systemic toxicity of i.v. Bevacizumab, we have begun a Phase I clinical trial to test the safety of transient blood brain barrier disruption with intraarterial (IA) Mannitol followed by superselective intraarterial cerebral infusion (SIACI) of Bevacizumab. This case report describes the technical aspects of this procedure and its associated benefits and risks. This novel delivery method, which may herald the revival of Interventional Neuro-oncology, may significantly alter the way therapy is administered to patients with GBM.