Treatment of glioblastoma multiforme (GBM), a primary malignant tumor of the brain, is one of the most challenging problems as no currently available treatment is curative. Surgery remains the basic treatment in which the bulk of the tumor is removed and the peripheral infiltrating part is the target of supplementary treatments. The currently available anticancer therapeutics have less than optimal usefulness for GBM, mainly owing to delivery problems to the tumor, including those due to blood-brain barrier. Several new therapies in development for GBM will require innovative methods of delivery besides the current practice of direct introduction of drugs and devices into the tumor. Nanobiotechnology, particularly nanoparticles, is making a significant contribution to the improvement of drug delivery in cancer and many of these technologies can be applied to GBM. Nanobiotechnology can provide a platform for combination of diagnostics, therapeutics, and its delivery to the tumor with subsequent monitoring of response. These technologies are reviewed and the prospects of improvement of therapeutic delivery to the brain are excellent during the next 5 years. Curing of GBM, however, depends on discovery of an anticancer agent that will destroy GBM completely.