The gut is the largest producer of serotonin or 5-hydroxytryptamine (5-HT) in the human body, and 5-HT has been recognized as an important signaling molecule in the gut for decades. There are two distinct sources of enteric 5-HT. Mucosal 5-HT is predominantly produced by enterochromaffin (EC) cells of the gastrointestinal (GI) tract, and neuronal 5-HT in the gut is produced by serotonergic neurons of the enteric nervous system (ENS). The quantity of mucosal 5-HT produced vastly eclipses the amount of neuronal 5-HT in the gut. Though it is difficult to separate the functions of neuronal and mucosal 5-HT, in the normal gut both types of enteric 5-HT work synergistically playing a prominent role in the maintenance of GI functions. In inflammatory conditions of the gut, like inflammatory bowel disease (IBD) recent studies have revealed new diverse functions of enteric 5-HT. Mucosal 5-HT plays an important role in the production of pro-inflammatory mediators from immune cells, and neuronal 5-HT provides neuroprotection in the ENS. Based on searches for terms such as “5-HT”, “EC cell”, “ENS”, and “inflammation” in pubmed.gov as well as by utilizing pertinent reviews, the current review aims to provide an update on the role of enteric 5-HT and its immune mediators in the context of intestinal inflammation.