We evaluate genetic, behavioral, developmental and experiential risk factors for primary adult brain tumors (primarily, astrocytoma and meningioma) using a systematic set of principles adapted from evidence-based medicine standards. In addition to ionizing radiation, rare mutations in highly penetrant genes associated with certain diseases/syndromes, and epilepsy and seizures (which probably result from, rather than cause, adult brain tumors), only the unexplained observation of familial aggregation of astrocytoma has been consistently shown. There is promising renewed interest in associations between infections, allergic conditions and adult brain tumor risk. Our knowledge of the causes of adult brain tumors is limited and should be expanded by results from large, well-designed studies of novel potential risk factors and potential interactions between known and suspected risk factors.