This mini-review addresses the role of the neuroendocrine substance serotonin (5-hydroxytryptamine, 5-HT) in intestinal luminal sensing and secretion. Intestinal sensory neurones are activated by several mechanisms, in particular following stimulation of 'specialized' cells in the mucosa. These specialized cells are the enteroendocrine cells, which contain a wide variety of neuroendocrine transmitters. One of these enteroendocrine cells is the enterochromaffin (EC) cell, which is present throughout the intestines and contains large amounts of serotonin, predominantly in the duodenum in humans. The EC cells act as mucosal sensory transducers and secrete serotonin in response to various physiological and pathological luminal stimuli. Following release, serotonin participates in several mucosal protecting processes, one being secretion. Serotonin stimulates active ion, mucus and fluid secretion. Epithelial 5-HT(2) receptors and neuronal 5-HT(1P), 5-HT(3) and 5-HT(4) receptors mediate the secretory effect of serotonin. A transmembrane serotonin transporter terminates epithelial serotonergic signalling. The transient receptor potential ion channel family is important for processing intestinal luminal sensory signalling. Accumulating evidence suggests a significant interaction between serotonin and one of the transient receptor potential ion channels, the capsaicin-sensitive transient receptor potential vanilloid type 1. Accordingly, EC cells, serotonergic receptors and transporter(s), and transient receptor potential vanilloid type-1 ion channels are all explored as pharmacological targets for treatment of some intestinal functional disorders.