Non-sugar sweeteners have been developed as an alternative to sugars and are widely used both as an ingredient in pre-packaged foods and beverages and added to food and beverages directly by the consumer. Individual non-sugar sweeteners undergo toxicological assessment by the by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and other authoritative bodies to establish safe levels of intake (i.e. acceptable daily intake or ADI). While results of randomized controlled trials have generally suggested non-sugar sweeteners may have little impact on glucose metabolism and result in lower body weight when coupled with energy restriction in the short-term, there is no clear consensus on whether non-sugar sweeteners are effective for long-term weight loss or maintenance, or if they are linked to other long-term health effects at intakes within the ADI. This systematic review brings together the most current scientific evidence on health effects of non-sugar sweetener use.