Technical Abstract: The gastrointestinal (GI) tract is the largest interface between an animal’s internal milieu and its exterior environment. As such, it forms a physical barrier between both environments. However, the function of the GI tract in the well-being of an animal is more complex than this passive role. The GI tract not only regulates the selective entry of nutrients while keeping vigilant against pathogens but also is largely responsible for shaping the immune response. Through specialized receptors and other more general mechanisms, the GI tract is not only able to sense changes in its environment but also to actively respond to these changes. These responses allow the intestine to contribute to the defense against microbes and to the control and regulation of the local immune response. In addition, the luminal microbial ecosystem is a highly complex community of primarily bacterial microbes that communicates extensively both with itself and the host. This microbial community has major influences on the host, including effects upon nutrient absorption, cancer, inflammation, host metabolism, barrier function, gut function (neuromotor, immunologic, and vascular), among others. The regulation of the immune response is the basis for the use of probiotics and prebiotics reviewed in this chapter.