Among pediatric malignancies, medulloblastoma (MB) is one of the most common malignant tumors of the CNS. In the past few years, thanks to a multidisciplinary approach including surgery, chemo- and radiation therapy, survival has significantly improved. Despite that, a third of patients still have a low chance of being cured and long-term survivors experience severe treatment-related sequelae. MBs are usually classified according to a clinical risk stratification, based on histological features, age at diagnosis, extent of tumor resection and presence or absence of metastases. However, these clinical variables have recently been reported to be poor for defining risk-related disease. Retrospective studies have identified histological or biological factors that have distinct roles in prognosis. As several pathways have been discovered to be involved in MB pathogenesis, they should be taken into account to more accurately stratify patients and their treatment and to develop innovative therapies.