High-grade gliomas, in particular anaplastic astrocytoma and glioblastoma multiforme, represent two of the most devastating forms of brain cancer. In spite of the poor prognosis, new treatments and emerging therapies are making an impact on this disease. This review discusses the role of the surgical management of high-grade gliomas and provides an overview of the currently available therapies which depend on surgical intervention. At the same time, cutting-edge clinical trials for patients with malignant brain tumors are reviewed to provide further insights into potential future therapies.