OBJECTIVE To investigate the evidence for sealants as a means to prevent caries in children and adolescents and, in the presence of suitable supporting evidence, to develop a protocol for the application of sealants. 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 303 articles were identified by the literature search; relevance was determined by examining the title and abstract of the articles. Thirty-eight original research studies met the inclusion criteria. These articles were read in full and scored independently by 2 reviewers, and evidence was extracted for development of recommendations. CONCLUSIONS The following recommendations are based on the evidence gathered in this review: 1. Sealants should be placed on all permanent teeth without cavitation (i.e., teeth that are free of caries, teeth that have deep pit and fissure morphology, teeth with "sticky" fissures or teeth with stained grooves) as soon after eruption as isolation can be achieved. 2. Sealants should not be placed on partially erupted teeth or teeth with cavitation or caries of the dentin. 3. Sealants should be placed on the primary molars of children who are susceptible to caries (i.e., those with a history of caries). 4. Sealants should be placed on first and second molars within 4 years after eruption. 5. Resin-based sealants should be preferred, until such time as glass ionomer cements with better retention capacity are developed. 6. Sealants should be placed as part of an overall prevention strategy based on assessment of caries risk.