Malignant gliomas are among the most challenging of all cancers to treat successfully, being characterized not only by aggressive proliferation and expansion but also by inexorable tumor invasion into distant brain tissue. Although considerable progress has been made in the treatment of these tumors with combinations of surgery, radiotherapy, and chemotherapy, these efforts have not been curative. Neurosurgeons as oncologists have increasingly turned their attention to therapies on a molecular scale. Of particular interest to neurosurgeons is the ability to deliver therapy locally to the tumor site or to take advantage of existing immunological mediators, enhancing drug concentrations or therapeutic cell numbers while bypassing the blood-brain barrier to maximize efficacy and minimize systemic toxicity. Exciting local-therapy approaches have been proposed for these devastating tumors. In this review, we discuss the potential applications of bioreactors, neural stem cells, immunotherapies, biodegradable polymers, and convection-enhanced drug delivery in the treatment of malignant gliomas. These approaches are at different stages of readiness for application in clinical neurosurgery, and their eventual effects on the morbidity and mortality rates of gliomas among human patients are difficult to ascertain from successes in animal models. Nevertheless, we are entering an exciting era of "nanoneurosurgery," in which molecular therapies such as those discussed here may routinely complement existing surgical, radiological, and chemotherapeutic approaches to the treatment of neuro-oncological disease. The potential to deploy any of a number of eloquently devised molecular therapies may provide renewed hope for neurosurgeons treating malignant gliomas.