Several calcium-channel blockers currently in use for the treatment of cardiovascular disorders have recently been tested for their effects on gastrointestinal motility. The rationale for this approach centers on the concept that calcium-channel blockers are at least as potent in inhibiting intestinal smooth muscle as in relaxing vascular smooth muscle. This review will give an outline of the most recent findings on the role of calcium and calcium channels in smooth muscle and neuronal function in the digestive system. It will also consider the mechanisms by which calcium-channel blockers may affect gastrointestinal motility and assess potential clinical applications in gastroenterology. The main goal for researchers in this field will be the development of gut-selective agents, with no cardiovascular side effects.