Tremendous strides have been made in both the treatment and the biologic understanding of medulloblastoma. Present optimal treatment can cure most medulloblastoma patients. A substantial minority of patients, however, will have recurrent or progressive disease. Recent studies have demonstrated that the success of treatment is not simply a matter of chance, but rather can be predicted based on specific biologic markers. These markers predict outcome independent of clinical staging and make clear that medulloblastomas are a biologically diverse group of tumors with variable clinical behavior. Molecular biologic investigation, including replication of tumorigenesis in transgenic mice, has further elucidated the complex biology of medulloblastoma. Current standard and investigational treatments, however, do not yet make use of biologic markers that predict risk of recurrence. Practical limitations have slowed the pace at which treatment paradigms can be revised to incorporate biologic insights. Mouse medulloblastoma models may provide an important bridge between biologic investigation and the development of new therapeutic approaches.