The taste of sweeteners is hedonically pleasing, suggests high caloric value in food, and contributes to increased intake. In recent years, many of the molecular mechanisms underlying the detection of sweeteners have been elucidated. Of particular note is the identification of the sweet taste receptor, the heteromeric G-protein-coupled receptor T1R2:T1R3, which responds to a vast array of chemically diverse natural and artificial sweeteners. In this chapter, we discuss some of the mechanisms underlying the detection of sweeteners by mammals, with a particular focus on the function and role of the T1R2:T1R3 receptor in these processes.