Serotonin (5-HT) plays a critical role in the regulation of gastrointestinal motility, secretion and sensation. Serotonin is secreted by enterochromaffin (EC) cells and acts on receptors located on smooth muscles, enterocytes and nerves (5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT7). Enterocytes express the serotonin reuptake transporter (SERT), which terminate the action of 5-HT. There are lines of evidence that functional gastrointestinal disorders, as irritable bowel syndrome (IBS), are associated with defective enteric serotonergic signaling. Plasma level and mucosal cells containing EC are increased in diarrhea predominant IBS. Serotonin reuptake transporter expression in colonic mucosa is significantly reduced in IBS. Moreover, 5-HT receptor agonists and antagonists seem to be effective in the treatment of symptoms of IBS. 5-HT3 receptor antagonists--alosetrone, granisetrone, ondansetrone--modulate visceral sensitivity and slow intestinal transit. They have proved to be effective in diarrhea predominant IBS. 5-HT4 agonists--tegaserode, prucalopride--relieve abdominal pain and bloating and improve intestinal transit in constipation predominant IBS. 5-HT4 antagonist--piboserode--is being investigated for a diarrhea predominant IBS.