The identification of molecular genetic abnormalities in specific types of pediatric brain tumors is beginning to play a role in the stratification of patients into treatment groups. The finding of an INI1 alteration in an atypical teratoid/rhabdoid tumor or malignant neoplasm with overlapping histologic features will be required for entry onto disease-specific protocols within the Children's Oncology Group. Refinement in the classification of medulloblastoma and malignant glioma patients will likely depend on the genetic and signaling pathways that characterize these tumors. Advances in this area will depend on the ability to identify new disease genes, validate prognostic markers, and develop biologically based therapeutic strategies to tailor treatment.