PURPOSE OF REVIEW: The current review summarizes and discusses current knowledge on sweeteners and sweetness enhancers. RECENT FINDINGS: The perception of sweet taste is mediated by the type 1 taste receptor 2 (T1R2)/type 1 taste receptor 3 (T1R3) receptor, which is expressed in the oral cavity, where it provides input on the caloric and macronutrient contents of ingested food. This receptor recognizes all the compounds (natural or artificial) perceived as sweet by people. Sweeteners are highly chemically diverse including natural sugars, sugar alcohols, natural and synthetic sweeteners, and sweet-tasting proteins. This single receptor is also the target for developing novel sweet enhancers. Importantly, the expression of a functional T1R2/T1R3 receptor is described in numerous extraoral tissues. In this review, the physiological impact of sweeteners is discussed. SUMMARY: Sweeteners and sweetness enhancers are perceived through the T1R2/T1R3 taste receptor present both in mouth and numerous extraoral tissues. The accumulated knowledge on sugar substitutes raises the issue of potential health effects.