Medulloblastoma and supratentorial primitive neuroectodermal tumors (sPNETs) are embryonal brain tumors and are the most common malignant brain tumors in the pediatric population. Current therapy for these children most often includes a multi-modality approach including surgery, radiation and chemotherapy. With modern therapy, overall survival for medulloblastoma is approximately 80% while survival for sPNET is 30–50%. Factors associated with prognosis include the presence of disseminated disease, extent of surgical resection and patient age, with children <3 years categorized as high risk patients given the inability to deliver high dose radiation at this young age due to significant long term effects. Increasingly, there is great interest in further sub-grouping patients based on molecular profiling which is highly predictive of outcome. While four molecular subgroups have emerged for medulloblastoma, the sub-grouping of sPNET has proved more challenging with an increasing awareness that this is a heterogeneous group in which histological diagnosis is challenging. The current challenges for both medulloblastoma and sPNET include the determination of optimal therapy for children such as decreased therapy for favorable risk groups and intensification and targeted therapy for high risk groups. Additionally, data are now available for long-term survivors which detail the significant effects of therapy in this young population.