Middle-aged and older adults continue to experience new caries lesions at rates comparable to or greater than adolescents, and there continues to be a need to identify effective caries-preventive regimens for adults. Both professionally-applied and self-applied preventive methods represent feasible approaches to reducing the burden of oral disease. This Quality Resource Guide (QRG), using an evidence-based approach, reviews the mode of action and the multifunctional role of fluoride in adult patients’ oral health care and its caries preventive action. It discusses the role of fluoride in the treatment of early (initial) and recurrent caries lesions and the different modalities of fluoride therapy available for adults. Choosing appropriate fluoride therapy approaches to reduce the incidence of coronal and root caries in caries-active adults is outlined, including self-applied (toothpastes, mouthrinses, gels) and professionally-applied (varnish, gels/foams, silver diamine) products. This QRG will serve as an important resource for the dentist, and all members of the office staff, as they assess and provide therapy for caries-active adults within the practice.