The role of viral infection in the etiology of febrile seizures is a relatively neglected field of neurologic research. A National Institutes of Health Consensus Conference (1981) omitted reference to causes of infections and the role of fever in febrile seizures, and emphasized outcome and anticonvulsant treatment. In an earlier review of the world literature (1924-1964), except for roseola infantum, viral infections as a cause of febrile seizures were rarely diagnosed. The present review includes reports of viruses most commonly associated with febrile seizures in the last decade, especially human herpesvirus-6 and influenza. The specificity and neurotropic properties of some viruses in the febrile seizure mechanism, a possible encephalitic or encephalopathic pathology, and the essential role of fever and height of the body temperature as a measure of the febrile seizure threshold are discussed. Cytokine and immune response to infection, and a genetic susceptibility to febrile seizures are additional etiologic factors. Future research should emphasize early detection of causative viruses, the nature of viral neurotropism, and the role of cytokines in fever induction. Trials of antiviral agents and vaccines, with attention to safety concerns, and more effective antipyretics would address the febrile seizure mechanism more specifically than anticonvulsant therapies.