The primary function of the gastrointestinal (GI) tract is the extraction of nutrients from the diet. Therefore, the GI tract must possess an efficient surveillance system that continuously monitors the luminal content for beneficial or harmful compounds. Recent studies have shown that specialized cells in the intestinal lining can sense changes in this content. These changes directly influence fundamental GI processes such as secretion, motility, and local blood flow via hormonal and/or neuronal pathways. Until recently, most studies examining the control of ion transport in the colon have focused on neural and hormonal regulation. However, study of the regulation of gut function by the gut chemosensory system has become increasingly important, as failure of this system causes dysfunctions in host homeostasis, as well as functional GI disorders. Furthermore, regulation of ion transport in the colon is critical for host defense and for electrolytes balance. This review discusses the role of the gut chemosensory system in epithelial transport, with a particular emphasis on the colon.