The use of topically applied fluoride has been widely researched as a means to reduce the risk of dental caries in conjunction with other treatment modalities (mechanical oral hygiene, dietary control, antimicrobial intervention, pit and fissure sealants). There is overwhelming evidence that reports not only the significance and importance of the use of fluoride as a caries-preventive agent, but also how safe fluoride application is when used appropriately, particularly in higher risk individuals and populations. This paper reviews the caries-protective benefits of topical fluoride application in children and adolescents, with an emphasis on the clinical efficacy and safety of the vehicles by which fluoride is topically delivered. Fluoride toothpaste represents today the most cost-effective fluoride-delivery system in the oral cavity and its use should be the centerpiece in all caries-preventive strategies. On the other hand, mouthrinses, gels and varnishes currently represent adjuncts to toothpaste use and should be targeted towards individuals and groups at high risk of caries.