Over the past decades considerable advances have been made in neurosurgery, radiotherapy and chemotherapy resulting in improved survival and cure rates for children with brain tumors. Here we review four of the most common subtypes of pediatric brain tumors, low-grade and high-grade astrocytomas, medulloblastomas and ependymomas, highlighting their molecular features regarding their tumor biology, and promising potential therapeutic targets that may hold promise for finding new “molecular targeted” drugs. Importantly, appropriate clinical trial design will play a critical role in the evaluation of new and novel treatment approaches for pediatric brain tumors. J. Cell. Physiol. 217: 584–589, 2008. © 2008 Wiley-Liss, Inc.