Most aspects of the normal organisation and functioning of the enteric nervous system have been resolved in recent years, especially for the small and large intestines, where the ENS has essential roles in controlling bowel movement and transmucosal fluid exchange. The roles of the ENS in the esophagus are not understood, and the relative roles of intrinsic reflexes in relation to extrinsic control of the stomach require clarification. In the small intestine and colon, it needs to be understood how neural activity is orchestrated to subserve different functional outcomes, for example propulsion, mixing and retrograde movement. However, the most important future challenges are to properly understand the molecular and cellular changes that underlie enteric neuropathies, to utilise knowledge of the normal neurochemistry, pharmacology and physiology of the ENS to devise strategies to treat disorders of motility and secretion, and to develop effective therapeutic compounds. It is suggested that ion channels of enteric neurons have been under-investigated as therapeutic targets. Other future challenges lie in the identification of biomarkers for functional bowel disorders and in the use of neural stem cells for restitution of ENS function.