Interactions between the enteric nervous system of the gut and the brain occur bidirectionally over sympathetic and parasympathetic pathways. Coordinated actions of the central, autonomic and enteric nervous systems modulate intestinal motor, sensory and secretory activities by neuromodulators, including 5-HT, noradrenaline and dopamine. 5-HT is an important signaling molecule in the brain–gut axis and the 5-HT released from enterochromaffin cells modulates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. Irritable bowel syndrome is associated with altered motility, secretion and sensation; enteric 5-HT signaling may be defective in this disorder. In this editorial, recent data are reviewed and the potential for the development of pharmacologic intervention is assessed.