Glioblastoma (GBM) is the most important primary brain tumor, both in terms of its incidence and its devastating impact on the unfortunate patients who have it. Although several well-defined hereditary syndromes predispose to malignant gliomas, most cases occur in the absence of a such a syndrome. The role of environmental factors, based on the known associations to date, also appears limited when compared with the total number of patients affected. It is clear that much remains to be discovered to better elucidate the causes of GBM, but the increasing recognition of molecular subtypes may help advance this field. This review highlights current insights into the molecular epidemiology of GBM.