Serotonin or 5‐hydroxytryptamine (5‐
HT) is a neurotransmitter and hormone that contributes to the regulation of various physiological functions by its actions in the central nervous system ( CNS) and in the respective organ systems. Peripheral 5‐ HTis predominantly produced by enterochromaffin ( EC) cells of the gastrointestinal ( GI) tract. These gut‐resident cells produce much more 5‐ HTthan all neuronal and other sources combined, establishing ECcells as the main source of this biogenic amine in the human body. Peripheral 5‐ HTis also a potent immune modulator and affects various immune cells through its receptors and via the recently identified process of serotonylation. Alterations in 5‐ HTsignalling have been described in inflammatory conditions of the gut, such as inflammatory bowel disease. The association between 5‐ HTand inflammation, however, is not limited to the gut, as changes in 5‐ HTlevels have also been reported in patients with allergic airway inflammation and rheumatoid arthritis. Based on searches for terms such as ‘5‐ HT’, ‘ ECcell’, ‘immune cells’ and ‘inflammation’ in pubmed.gov as well as by utilizing pertinent reviews, the current review aims to provide an update on the role of 5‐ HTin biological functions with a particular focus on immune activation and inflammation.