Advances in the field of small-bowel motility in the last few years include the delineation of the role of the intrinsic primary afferent neuron in eliciting the peristaltic reflex, the genetic control of the development of the enteric nervous system, and the potential role of the interstitial cells of Cajal as pacemakers of the intestine and colon. New promising molecules have been developed for therapeutic purposes, particularly in the modulators of serotonin receptors. Their effects on sensory and motor function has allowed a better recognition of the important role of 5-hydroxytryptamine in several disorders, especially in irritable bowel syndrome. In this brief review, we have elected to appraise the advances pertaining to human studies, with emphasis on novel methodologies, disease manifestations, and novel therapeutic strategies.