Glioblastoma is the most common intracranial malignancy in adults and carries a poor prognosis. Chemotherapeutic treatment figures prominently in the management of primary and recurrent disease. However, the blood-brain barrier presents a significant and formidable impediment to the entry of oncotherapeutic compounds to target tumor tissue. Several strategies have been developed to effect disruption of the blood-brain barrier and in turn enhance the efficacy of cytotoxic chemotherapy, as well as newly developed biologic agents. Focused ultrasonography is one such treatment modality, using acoustic cavitation of parenterally administered microbubbles to mechanically effect disruption of the vascular endothelium. We review and discuss the preclinical and clinical studies evaluating the biophysical basis for, and efficacy of, focused ultrasonography in the enhancement of oncotherapeutic agent delivery. Further, we provide some perspectives regarding future directions for the role of focused ultrasound in facilitating and improving the safe and effective delivery of oncotherapeutic agents in the treatment of glioblastoma.