OBJECTIVE: To develop a scientifically current and evidence-based protocol for the use of fluoride varnish for the prevention of dental caries among high-risk children and adolescents. METHODS: Previous systematic reviews on this topic were used as the basis for the current review. Ovid MEDLINE, CINAHL and several other relevant bibliographic databases were searched for English-language articles, with human subjects, published from 2000 to 2007. RESULTS: A total of 105 articles were identified by the literature search; relevance was determined by examining the title, abstract and body of the article. Seven original research studies met the inclusion criteria, These articles were read and scored independently by 2 reviewers, and evidence was extracted for systematic review.