The clinical features of pediatric brain tumors have been well characterized, and a specific histopathological classification exists (W.H.O. classification, 2007) that allows stratification into treatment regimens and permits a prediction of natural history. Our understanding of the molecular pathobiology of pediatric brain tumors and its clinical correlates remains an area of active research that holds the promise of improved diagnosis, therapy, and prognostic determination. Certainly, key examples in the literature point to the impact that a molecular approach to the understanding of tumor response to therapy can have on patient management. For example, adults and children with malignant gliomas that demonstrate a DNA hypermethylation phenotype, resulting in repression of the O6-methylguanine-DNA methyl transferase (MGMT) gene, have a greater probability of survival when treated with the alkylating agent temozolamide (1). Another example of molecular diagnosis and prognosis in human brain tumors is the finding of an enhanced chemotherapy response and survival advantage of 1p and 19q co-deletion resulting from an unbalanced translocation in oligodendroglioma. Molecular understanding of tumor cell processes can have a significant impact on the development of novel therapies. This has been the case for chronic myeloid leukemia in which identification of the Philadelphia chromosome led to the discovery of a unique translocation that resulted in a constitutively active kinase which gave cells a proliferative advantage (4). These findings subsequently led to the development of tyrosine kinase inhibitors that have been used to treat chronic myeloid leukemia and acute lymphoblastic leukemia with a dramatic improvement in clinical outcome for patients harboring the Philadelphia chromosome (6). Advances in the molecular understanding of pediatric brain tumor pathobiology have not as yet resulted in a magic bullet therapy. It is the author’s impression that given the complex nature of biological signaling systems and the growing understanding of the genetic diversity in pediatric brain tumors, no single therapy will be effective for all types of tumors or even for all tumors that look the same when the W.H.O. classification criteria are applied.