In this review we provide evidence for the existence of genes associated with primary malignant brain tumors. We summarize the current knowledge from studies of familial cancer aggregation, hereditary syndromes, and molecular and cytogenetic studies. The epidemiologic evidence is suggestive but inconclusive for an association between brain tumors and cancers in other family members, including cancers of the breast, lung and colon. Central nervous system (CNS) tumors have been associated with several hereditary syndromes including the Li-Fraumeni cancer family syndrome, neurofibromatosis (types 1 and 2), tuberous sclerosis, nevoid basal cell carcinoma syndrome, familial polyposis, and von Hippel-Lindau disease. Significant studies leading to the recognition of molecular and cytogenetic abnormalities in malignant gliomas are described in detail. The genetic studies conducted thus far suggest a role for inherited susceptibility in some CNS tumors.