Metoclopramide is a stimulant of upper gut motility and an anti-emetic. The mechanisms by which the drug exerts these actions has been the subject of considerable research, which is briefly reviewed in this article. From the viewpoint of drug discovery, the properties of metoclopramide have directly led to the development of selective gut motility stimulants and 5-HT3 receptor antagonists. These events and the potential clinical use of such compounds are reviewed in detail.