The long-term survival of children with brain tumor has improved considerably in the last three decades, owing to advances in neuroimaging, neurosurgical, and radiation therapy modalities, coupled with the application of conventional chemotherapy. MRI, MR spectroscopy and diffusion-weighted MRI have contributed to more accurate diagnosis, prognostication and better treatment planning. Neurosurgical treatment has been advanced by the use of functional MRI, and intraoperative image-guided stereotactic techniques and electrophysiologic monitoring. The use of 3-D conformal and intensity-modulated radiation therapy, stereotactic radiosurgery, and radiosensitizing agents has made radiation therapy safer and more effective. Conventional chemotherapy, administered either alone or combined with radiation therapy has improved survival and quality of life of children with brain tumors. These improved outcomes have also occurred, due, in part, to their treatment on collaborative national and international studies. Recent promising diagnostic and therapeutic strategies have resulted from advances in understanding molecular brain tumor biology. Important new approaches include the refinement of drug-delivery strategies, the evaluation of biologic markers to stratify patients for optimal treatment and to exploit these molecular differences using "targeted" therapeutic strategies. These approaches include blocking tumor cell drug resistance mechanisms, immunotherapy, inhibition of molecular signal transduction pathways important in tumorigenesis, anti-angiogenic therapy, and gene therapy. The thrust of such approaches for children with brain tumors is especially directed at reducing the toxicity of therapy and improving quality-of-life, as well as increasing disease-free survival.