The gastrointestinal tract serves the physiological function of digesting and absorbing nutrients from food and physically mixing and propelling these contents in an oral to anal direction. These functions require the coordinated interaction of several cell types, including enteric nerves, immune cells and smooth muscle. Interstitial cells of Cajal (ICC) are now recognized as another cell type that are required for the normal functioning of the gastrointestinal tract. Abnormalities in ICC numbers and networks are associated with several gastrointestinal motility disorders. This review will describe what is known about the function and role of ICC both in health and in a variety of motility disorders with a focus on unresolved issues pertaining to their role in the control of gastrointestinal motility.