The intestinal epithelium is a major interface with the outside world. This interface is separated from the body’s internal milieu by a single layer of epithelial cells consisting of absorptive enterocytes, goblet, enteroendocrine and Paneth cells. These cells are exposed, at the luminal domain, to an external environment that is continuously changing by types and amounts of nutrients, microorganisms, microbial products, gastrointestinal secretions and potentially toxic chemicals. The intestinal epithelium constantly monitors the composition of its contents to optimize nutrient absorption, as well as defending threats to its integrity. In recent years significant advances have been made in the understanding of the molecular recognition events involved in sensing the luminal contents of the gastrointestinal tract. The sensing of various nutrients in the gastrointestinal tract is accomplished by several G-protein coupled receptors, expressed on the luminal membrane of enteroendocrine cells. Sensing of nutrients by these receptors leads to secretion of hormones that control vital physiological functions such as food intake, nutrient digestion and absorption, intestinal barrier function and insulin secretion. The intestine also contains approximately 1000 different species of bacteria and has to discriminate between pathogenic and commensal bacteria to maintain a balance between immune protection and inflammatory over-reactions. A class of proteins known as pattern recognition receptors, in particular toll-like receptors (TLRs 1–10) play a key role in the recognition of microbes via detection of conserved molecular features. The sensory receptors that face the lumen of the intestine and are responsive to luminal contents provide a unique therapeutic opportunity. In my talk I will present data on the role of the gut expressed taste 1 receptor (T1R) family in intestinal nutrient sensing and the contribution of TLR9-recognition of bacteria in control of gut hormone release. The impact of these findings to animal nutrition will be discussed.