Immune mechanisms play a critical role in systemic disorders (systemic lupus erythematosus, Sjögren's syndrome, Crohn's disease, and sarcoidosis) and in localized central nervous system (CNS) disorders (CNS vasculitis, multiple sclerosis, acute disseminated encephalomyelitis, and encephalitides). Both humoral and cell-mediated mechanisms are involved in the systemic and CNS-limited disorders. Immune mechanisms may also be a factor in a number of epilepsies such as Rasmussen's encephalitis, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and temporal lobe epilepsy. Immunologic abnormalities are found in routine epilepsy surgical specimens, suggesting a broader role of immunopathology in the etiology of epilepsy. The prevalence and impact of immunopathology in epilepsy syndromes remains to be determined by future research.