The gut endocrine system comprises a collection of enteroendocrine cells scattered through the intestinal epithelium. Enteroendocrine cells detect the local luminal composition and release hormones that regulate post-prandial physiology, including gut motility/secretion, and regulation of insulin secretion and food intake. They can detect a wide variety of ingested nutrients, via a range of sensory proteins that detect the digestion products of carbohydrates, fats and protein. Most enteroendocrine cells have an apical surface facing into the gut lumen, and express sodium and proton-coupled nutrient transporters typical of the intestinal brush border. Electrogenic transporter-mediated uptake of monosaccharides, amino acids and di/tripeptides generates electrical signals that trigger membrane depolarisation, voltage gated calcium entry and hormone release. Other stimuli are detected by enteroendocrine-specific G-protein coupled receptors, including free fatty acid receptors (FFA1-4), bile acid receptors (GPBAR1) and mono-acylglycerol receptors (GPR119), that activate Gq and Gs dependent signalling pathways and thereby modulate calcium and cAMP concentrations. Gut hormones have proven translational value in the therapeutics of diabetes, obesity and short bowel syndrome, and are dramatically altered after gastric bypass surgery. It is hoped that further exploitation of the enteroendocrine system will lead to the development of new therapies for diabetes and obesity.