The enteric nervous system (ENS) is intrinsic to the gastrointestinal (GI) tract and controls essential gut functions such as motility, blood flow and secretions. Injury to the ENS contributes to the pathophysiology of common GI disorders including irritable bowel syndrome and the inflammatory bowel diseases. Recent data show that enteric glia, a type of peripheral glia that surround enteric neurons, contribute to neuroinflammation and express major histocompatibility complex class II (MHC II) during disease.