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Multimodal treatment consisting of surgery, radiation therapy, and chemotherapy reduced cumulative incidence of late mortality but increased the incidence of subsequent neoplasms and severe, incapacitating chronic health conditions. Present treatment strategies fail to recognize heterogeneity within patients despite wide divergence in individual responses. The persistent mortality rates and serious side effects of non-targeted cytotoxic therapies indicate a need for more refined therapeutic approaches. Advanced genomic research has led to the accumulation of an enormous amount of genetic information and resulted in a consensus distinguishing four molecular subgroups, WNT-activated, SHH-activated, and Group 3 and 4 medulloblastomas. These have distinct origin, demographics, molecular alterations, and clinical outcomes. Although subgroup affiliation does not predict response to therapy, new subgroup-specific markers of prognosis can enable a more layered risk stratification with additional subtypes within each primary subgroup. Here, we summarize subgroup-specific genetic alterations and their utility in current treatment strategies. The transition toward molecularly targeted interventions for newly diagnosed MBs remains slow, and prospective trials are needed to confirm stratifications based on molecular alterations. At the same time, numerous studies focus at fine-tuning the intensity of invasive radio- and chemotherapies to reduce intervention-related long-term morbidity. There are an increasing number of immunotherapy-based treatment strategies including immune checkpoint-inhibitors, oncolytic viruses, CAR-T therapy, and NK cells in recurrent and refractory MBs. 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Taylor, M.D., Northcott, P.A., Korshunov, A., Remke, M., Cho, Y.J., Clifford, S.C., Eberhart, C.G., Pfister, S.M., Molecular subgroups of medulloblastoma: The current consensus (2012) Acta Neuropathologica, 123 (4), pp. 465-472 ", "listPosition" : 7, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2591444, "link" : "/api/reference/2591444", "label" : "8. Northcott, P.A., Buchhalter, I., Morrissy, A.S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., Gröbner, S., Lichter, P., The whole-genome landscape of medulloblastoma subtypes (2017) Nature, 547 (7663), pp. 311-317 ", "listPosition" : 8, "published" : false, "snippet" : true }, { "otype" : "Reference", "mtid" : 2591445, "link" : "/api/reference/2591445", "label" : "9. Northcott, P.A., Jones, D.T., Kool, M., Robinson, G.W., Gilbertson, R.J., Cho, Y.J., Pomeroy, S.L., Pfister, S.M., Medulloblastomics: The end of the beginning (2012) Nature Reviews. 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