The role of melatonin in the gastrointestinal (GI) tract had previously been limited to its well-described anti-oxidant properties. Recent studies have, however, expanded the role of melatonin in the intestine, showing that it acts as a hormone with local paracrine actions to modulate GI function and the release of other hormones. The GI epithelium produces melatonin from the active precursor serotonin, which is thought to come from the serotonin synthesising enterochromaffin cells (EC). The receptors for melatonin, the membrane bound melatonin receptors 1 and 2, are present on some smooth muscles, neurons, and epithelium. Endogenous release of melatonin has been linked with secretory reflexes and the ileal brake reflex, while exogenous application of melatonin in pharmacological doses has been associated with reduced inflammation in a variety of animal models. Recent studies have begun to look at melatonin release from the GI epithelium using real-time electrochemical detection methods. Using these techniques, the time course of melatonin production shows similarities to that of 5-HT release while the ratio of 5-HT to melatonin is altered during aging. In addition, the effects of melatonin supplementation on the production of endogenous melatonin and its precursor serotonin are suppressed. In summary, the role of melatonin in the GI tract is coming of age. There are many studies showing a clear role for endogenously produced melatonin and clear effects of melatonin supplementation. Newly developed electrochemical techniques for exploring melatonin availability in real-time promise to accelerate our understanding of GI melatonin in the years to come.