This chapter reviews current research related to the aetiopathology of irritable bowel syndrome (IBS). IBS is a heterogeneous disorder and likely encompasses many pathogenic processes. Visceral hypersensitivity to rectal distension is considered a hallmark for IBS and is found in 30"–90" patients with IBS, where it is associated with more severe symptomatology. Intestinal secretion is regulated by epithelial enteroendocrine cells that release peptides and amines in response to luminal factors. The predominant neurotransmitter is serotonin, which influences the enteric nervous system (ENS) and impacts upon intestinal motility, vasodilatation and secretion. Up to one third of patients with IBS report a relative with IBS and twin studies suggest the genetic heritability is 22"–57". Mast cells are intimately co-located with enteric neurons with an increased density in patients with IBS. Bile acids promote secretion from colonic epithelium, stimulate propagating pressure waves in colon and result in a reduction in visceral sensory thresholds, physiological changes which are commonly seen in IBS.