Malignant astrocytomas are infiltrative and aggressive brain tumors. Conventional forms of therapy have not been effective in controlling this incurable disease. Recent advances in understanding the molecular biology of these tumors have revealed potential mechanisms by which astrocytoma cells undergo tumor initiation, progression, and maintenance, as well as possible avenues for targeted therapeutics. Studies on the role of neural stem cells as cells of origin and tumor-propagating cells have also greatly increased our understanding of the biology and clinical behavior of these tumors. An integrated view of the genetics, signal transduction, and cell biology of astrocytomas, as well as clinical data from patients, will provide a more useful approach in designing novel therapies for this devastating disease.