Clinical experiments were performed to investigate the effect of fluoride on carious lesion development and on lesions established during fixed orthodontic therapy. All presently available fluoride agents are developed from the concept of fluoridating the enamel in the form of fluorhydroxyapatite. Recent research has indicated, however, that calcium fluoride formation may be a major aspect of the mechanism of the cariostatic effect of topical fluoride. Therefore a fluoride solution with very low pH (1.9) that induced large amounts of calcium fluoride also was tested on lesion development underneath orthodontic bands. Daily fluoride mouth rinsing with a 0.2% solution sodium fluoride (NaF) retarded lesion development significantly, whereas the fluoride solution with low pH inhibited lesion formation completely. Fluoride applied as a mouth rinse to plaque-covered lesions underneath orthodontic bands retarded lesion progression. The remineralizing capacity of saliva was found to be rapid in the absence of any fluoride. Although white spot lesions may remineralize and even disappear, most of the emphasis should be directed against prevention of carious lesion development during treatment with fixed orthodontic appliances.