This paper examines the evidence demonstrating the effectiveness of sealants in high-caries-risk children and discusses the Research Triangle Institute/University of North Carolina's (RTI/UNC) systematic review. The strict RTI/UNC protocol limited the number of sealant studies that could be included. This analysis expanded their criteria to permit additional methods of determining caries risk (for example, past caries experience, less than two pairs of sound first permanent molars available/child in half-mouth designs) and outcome measures in addition to DMFS (that is, percent sealant retention, survival rates, cost-effectiveness, changes in salivary S. mutans levels). Nine clinical studies with a randomized, half-mouth, clinical trial design and seven studies with observational study designs were included. There is good evidence that sealants can be used efficaciously and effectively in high-risk children as long as the sealant is retained. Sealants are more effective in preventing further caries and providing cost savings in a shorter time span if placed in children who have high rather than low caries risk.