Serotonin (5-HT) is an important signaling molecule in the gut targeting enterocytes, smooth muscles and enteric neurons. Most of the body serotonin is present in enterochromaffin cells. Serotonin activates both intrinsic and extrinsic primary afferent neurons to, respectively initiate peristaltic and secretory reflexes and to transmit information to the central nervous system. Serotonin is inactivated by the serotonin reuptake transporter (SERT) in the enterocytes or neurons. Exogenous serotonin application evokes so many responses that it is difficult to determine which is physiologically relevant. This effect is largely due to the presence of multiple receptor subtypes, which appear to be present on several classes of myenteric neurons, on smooth muscle cells, and on epithelial cells. Irritable bowel syndrome (IBS) is a complex disorder that is associated with altered gastrointestinal motility, secretion and sensation. Altered serotonin signaling may lead to both intestinal and extra intestinal systems in IBS. In this review, the literature related to role of serotonin signaling in pathophysiology of IBS has been searched and summarized. Therapeutic agents targeting altered serotonin signaling may provide new effective treatment for patients with IBS. Tegaserod, 5-HT(4) partial agonist is used in constipation predominant IBS while alosetron, a 5-HT(3) antagonist used in IBS with diarrhea. Other compounds such as tricyclic antidepressants and serotonin selective reuptake inhibitors have been used in some patients with IBS.