In childhood and in adolescence, primary tumors of the central nervous system (CNS) are the second most common malignancy after leukemia. The most common entities are gliomas, craniopharyngiomas and embryonal tumors, including primitive neuroectodermal tumors of the CNS, such as medulloblastoma. Proper management of malignancies requires a histological diagnosis, especially in childhood, since diagnostic errors have a significant negative influence on the treatment and subsequently on the patient's care. Experimental research conducted in the last years regarding the genomic and epigenetic landscape of pediatric brain tumors has provided considerable help in understanding their pathogenesis. New mutations and new signaling pathways have been associated with pediatric neoplasia, according to recent studies. Current therapeutic protocols recommend triple therapy, consisting in the surgical resection of the tumor, radiotherapy and chemotherapy. However, the success of the therapy depends on the precociousness of establishing the diagnosis and initiating the treatment, age of the child, type of surgery (total∕partial), result of the histological examination, chemotherapy protocols and type of radiotherapy. Although immunotherapy and gene therapy continue to be a challenge, extensive studies are needed in order to confirm their promising role in the management of pediatric brain tumors.