Most of the 5-hydroxytryptamine (5-HT) present in the adult human body is located in the gastrointestinal tract. The vast majority is contained in enteroendocrine cells, the rest exists mainly in myenteric interneurons separated from the mucosa by an intraenteric barrier. Physiological studies suggest that 5-HT plays a vital role in mediating both sensory and reflex responses to gastrointestinal stimuli and, thus, this transmitter is closely implicated in gut reactions. This review outlines some of the evidence for different 5-HT receptors, summarizes the role of 5-HT in mediating gut sensitivity and motor activity, secretion and more complex activities, such as emesis and diarrhoea and identifies the clinical role of drugs acting on 5-HT receptors in the treatment of emesis, diarrhoea, the control of abdominal pain and discomfort and the rectification of gastrointestinal motility.