The gut contains large amounts of serotonin (5-HT) and this neuro-transmitter is now known to be intricately involved in the control of gastrointestinal physiological function via a number of receptor subtypes. The 5-HT3 and 5-HT4 receptors are currently the focus of much attention with respect to the therapy of irritable bowel syndrome (IBS) by the use of either agonists or antagonists. This article concentrates on the development of alosetron, cilansetron and tegaserod, highlighting the change in thinking that has to accompany the use of these new drugs, especially with regard to targeting subgroups and avoiding inappropriate prescription. It also raises the philosophical question of how safe drugs should have to be in this therapeutic area. © 2001 Prous Science. All rights reserved.