Brain tumors are currently diagnosed on the basis of their histology. The most common types in adults are astrocytomas, oligodendrogliomas and oligoastrocytomas or mixed tumors, which almost invariably lead to death. Improvements in outcome have been elusive despite intensive research. Recent findings indicate that response to conventional therapy, at least in some cases, correlates better with genetic characteristics than histopathology. An understanding of the molecular mechanisms that underlie the malignant phenotype of gliomas also provides the possibility of rational design of molecularly targeted therapies. This approach has proved successful in other areas of oncology. As many tumors have the same types of molecular abnormalities, molecular targeted therapies developed for nonbrain tumor types might be adapted for the treatment of brain tumors. There are a number of unique problems involved in treating tumors in the brain that must be overcome. The genetic predictors of response to conventional therapies, the genes and cellular mechanisms involved in glioma development, and potential therapeutic targets are reviewed. The possibility of designing tailored molecular therapy based on the molecular characteristics of the tumors is also explored.