Abstract The majority of the body's serotonin (5-HT) is produced by the gastrointestinal tract. 5-HT has several functions in the gastrointestinal tract. 5-HT is a paracrine signalling molecule released from enterochromaffin cells, a survival and proliferating factor and a neurotransmitter. The actions of 5-HT are transduced by a large family of 5-HT receptors, several of which are expressed on different gastrointestinal cell types including enteric nerves, smooth muscle and interstitial cells of Cajal (ICC). This review will summarize recent advances in understanding the role of 5-HT in regulating function of ICC, and the expression and function of 5-HT receptors on muscle and enteric nerves in human tissue. Rodent ICC express several 5-HT receptors including 5-HT2B receptors which regulate ICC survival and proliferation. Human smooth muscle and enteric neurons also express several 5-HT receptor subtypes. Expression and function of these receptors is significantly different from small laboratory animals. 5-HT7 receptor activation causes relaxation of muscle, whereas 5-HT2B receptors increase muscle activity. The 5-HT4 receptor appears to mediate both inhibition and activation of smooth muscle involving myogenic as well as neural actions. Despite the abundant expression of 5-HT3 receptors in the human enteric nervous system no functional correlate has been as yet demonstrated.