The gastrointestinal tract is a vast neuroendocrine organ with extensive extrinsic and intrinsic neural circuits that interact to control its function. Circulating and paracrine hormones (amine and peptide) provide further control of secretory, absorptive, barrier, motor and sensory mechanisms that are essential to the digestion and assimilation of nutrients, and the transport and excretion of waste products. Specialized elements of the mucosa (including enteroendocrine cells, enterocytes and immune cells) and the microbiome interact with other intraluminal contents derived from the diet, and with endogenous chemicals that alter the gut's functions. The totality of these control mechanisms is often summarized as the brain–gut axis. In irritable bowel syndrome (IBS), which is the most common gastrointestinal disorder, there may be disturbances at one or more of these diverse control mechanisms. Patients present with abdominal pain in association with altered bowel function. This review documents advances in understanding the pathophysiological mechanisms in the brain–gut axis in patients with IBS. It is anticipated that identification of one or more disordered functions in clinical practice will usher in a renaissance in the management of IBS, leading to effective therapy tailored to the needs of the individual patient.