Objective: Many scientists and laypeople alike have concerns about low‐calorie sweeteners (LCSs). These concerns stem from both a dissatisfaction with the taste of LCSs and reports that they cause metabolic disruptions (e.g., weight gain, glucose intolerance).

Methods: This article provides a critical review of the literature on LCSs from the standpoint of their taste, gastrointestinal, and metabolic effects; biological fate in the body; and impact on ingestion and glucose homeostasis.

Results and Conclusions: Mammals can readily discriminate between LCSs and sugars because both types of sweetener activate distinct oral and post‐oral sensory pathways. LCSs differ in their ability to access post‐oral tissues, but few studies have incorporated this observation into their design. It is difficult to extrapolate results between mice, rats, and humans because of interspecies differences in the taste and post‐oral actions of LCSs and the fact that investigators often use different response measures in rodents and humans. There is confounding in the experimental design of some of the most widely cited studies of LCS‐induced metabolic disruptions. The uncritical acceptance of these studies has generated considerable controversy. More work is needed to obtain a clearer understanding of the metabolic effects of LCSs.