The objective of this systematic review was to evaluate whether there is conclusive evidence that the professional application of fluoride varnish decreases the incidence of dental caries in preschool children. We searched the BBO, LILACS, MEDLINE and Cochrane electronic databases to identify controlled clinical trials that evaluated the development of cavitated caries lesions in children up to six years of age. Two researchers performed a critical appraisal of the studies selected for inclusion. Five-hundred and thirteen articles were found, but only eight met our inclusion criteria. Most of these eight studies were of poor methodological quality. They were also heterogeneous in relation to participants' previous caries experience, type of intervention performed on the control group, children's exposure to other sources of fluoride, and varnish application interval. The absolute differences between caries incidences in the control and test groups ranged from 0.30 to 1.64 and the preventive fractions varied from 5% to 63%. Fluoride varnish may be effective to decrease the incidence of dental caries in preschoolers, but more randomized clinical trials with better methodological quality are necessary to provide conclusive evidence in this respect.