This article presents evidence-based clinical recommendations for use of pit-and-fissure sealants developed by an expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs. The panel addressed the following clinical questions. Under what circumstances should sealants be placed to prevent caries? Does placing sealants over early (noncavitated) lesions prevent progression of the lesion? Are there conditions that favor the placement of resin-based versus glass ionomer cement sealants in terms of retention or caries prevention? Are there any techniques that could improve sealants’ retention and effectiveness in caries prevention? Staff of the ADA Division of Science conducted a MEDLINE search to identify systematic reviews and clinical studies published after the identified systematic reviews.