Gliomas of astrocytic, oligodendroglial and ependymal origin account for more than 70% of all brain tumors. The most frequent (65%) and most malignant histological type is the glioblastoma. Since the introduction of computerized tomography and magnetic resonance imaging, the incidence rates of brain tumors have been rather stable, with a tendency of higher rates in highly developed, industrialized countries. Some reports indicate that Caucasians have higher incidence than black or Asian populations, but to some extent, this may reflect socio-economic differences and under-ascertainment in some regions, rather than a significant difference in genetic susceptibility. With the exception of pilocytic astrocytomas, the prognosis of glioma patients is still poor. Less than 3% of glioblastoma patients are still alive at 5 years after diagnosis, higher age being the most significant predictor of poor outcome. Brain tumors are a component of several inherited tumor syndromes, but the prevalence of these syndromes is very low. Several occupations, environmental carcinogens, and diet (N-nitroso compounds) have been reported to be associated with an elevated glioma risk, but the only environmental factor unequivocally associated with an increased risk of brain tumors, including gliomas, is therapeutic X-irradiation. In particular, children treated with X-irradiation for acute lymphoblastic leukemia show a significantly elevated risk of developing gliomas and primitive neuroectodermal tumor (PNET), often within 10 years after therapy. TP53 mutations are frequent in low-grade gliomas and secondary glioblastomas derived therefrom. Approximately 60% of mutations are located in the hot spot codons 248 and 273, and the majority of these are G:C-->A:T transitions at CpG sites. TP53 mutations are significantly more frequent in low-grade astrocytomas with promoter methylation of the O(6)-methylguanine-DNA methyltransferase repair gene, suggesting that, in addition to deamination of 5-methylcytosine, exogenous or endogenous alkylation in the O(6) position of guanine may contribute to the formation of these mutations.