The role of the immune system in epilepsy is illustrated by pathological changes consistent with inflammation in surgical specimens excised from refractory epilepsy patients, various inflammatory mediators measured in the central nervous system of epilepsy patients, and recently by the discovery of new neuron-specific antibodies against plasma membrane proteins in encephalopathies and epilepsy. Both the innate immune system, consisting of cytokines and toll-like receptors, and adaptive immune system, in collaboration with anti-neuronal antibodies, are involved in neuroinflammation. Epidemiological studies indicating a close relationship between epilepsy and other systemic autoimmune disorders, and clinical response to immunomodulatory agents provide additional support for the involvement of inflammatory pathogenesis in epilepsy. Nevertheless, new studies are needed to establish the autoimmune and inflammatory theory as well as to define the clinical spectrum of autoimmune epilepsy.