The role of sugar substitutes such as xylitol and sorbitol in the prevention of dental caries has been investigated in several clinical studies. The purpose of this report is to review the current published evidence regarding the relationship between sugar substitutes and dental caries. A literature search was conducted using MEDLINE and EMBASE and included studies published from 1966 to 2001. Studies that included human subjects and were published in English were included in this review. A total of fourteen clinical studies were reviewed that evaluated the effect of sorbitol or xylitol or the combination of both sugar substitutes on the incidence of dental caries. Most of the reports were of studies conducted with children outside of the United States. These studies demonstrated a consistent decrease in dental caries, ranging from 30 to 60 percent, among subjects using sugar substitutes as compared to subjects in a control group. These caries rate reductions were observed in subjects using xylitol or sorbitol as the sugar substitute in chewing gum or toothpaste. The highest caries reductions were observed in subjects using xylitol. These findings suggest that the replacement of sucrose with sorbitol and xylitol may significantly decrease the incidence of dental caries.