Nonnutritive sweeteners (NNS) are ecologically novel chemosensory signaling compounds that influence ingestive processes and behavior. Only about 15% of the US population aged >2 y ingest NNS, but the incidence is increasing. These sweeteners have the potential to moderate sugar and energy intakes while maintaining diet palatability, but their use has increased in concert with BMI in the population. This association may be coincidental or causal, and either mode of directionality is plausible. A critical review of the literature suggests that the addition of NNS to non-energy-yielding products may heighten appetite, but this is not observed under the more common condition in which NNS is ingested in conjunction with other energy sources. Substitution of NNS for a nutritive sweetener generally elicits incomplete energy compensation, but evidence of long-term efficacy for weight management is not available. The addition of NNS to diets poses no benefit for weight loss or reduced weight gain without energy restriction. There are long-standing and recent concerns that inclusion of NNS in the diet promotes energy intake and contributes to obesity. Most of the purported mechanisms by which this occurs are not supported by the available evidence, although some warrant further consideration. Resolution of this important issue will require long-term randomized controlled trials.