While our knowledge of the dental caries process and its prevention has greatly advanced over the past fifty years, it is fair to state that the management of this disease at the level of the individual patient remains largely empirical. Recommendations for fluoride use by patients at different levels of caries risk are mainly based on the adage that more is better. There is a general understanding that the fluoride compound, concentration, frequency of use, duration of exposure, and method of delivery can influence fluoride efficacy. Two important factors are (1) the initial interaction of relatively high concentrations of fluoride with the tooth surface and plaque during application and (2) the retention of fluoride in oral fluids after application. Fluoride dentifrices remain the most widely used method of delivering topical fluoride. The efficacy of this approach in preventing dental caries is beyond dispute. However, the vast majority of currently marketed dentifrice products have not been clinically tested and have met only the minimal requirements of the FDA monograph using mainly laboratory testing and animal caries testing. Daily use of fluoride dental rinses as an adjunct to fluoride dentifrice has been shown to be clinically effective as has biweekly use of higher concentration fluoride rinses. The use of remineralizing agents (other than fluoride), directed at reversing or arresting non-cavitated lesions, remains a promising yet largely unproven strategy. High fluoride concentration compounds, e.g., AgF, Ag(NH3)2F, to arrest more advanced carious lesions with and without prior removal of carious tissue are being used in several countries as part of the Atraumatic Restorative Treatment (ART) approach. Most of the recent innovations in oral care products have been directed toward making cosmetic marketing claims. There continues to be a need for innovation and collaboration with other scientific disciplines to fully understand and prevent dental caries.