Highlights • The enteric nervous system (ENS) is the largest assembly of neurons and glia outside the central nervous system. • The ENS resides within the wall of the digestive tract and regulates local gut reflexes involved in gastrointestinal motility, blood flow and fluid transport. • Enteric glial cells are necessary and sufficient to modulate neuronal reflex circuits controlling gut motility. • Enteric glia respond to various neurotransmitters via increase in intracellular calcium and release of neuroactive substances, such as ATP through Cx43 hemichannels or Ca2+ -dependent exocytosis. • Enteric glial cells are actively involved in gut motility disorders and regulation of inflammation.