A large number of parameters will influence and mediate the activity and the pharmacological response of dental fluoride products after systemic or topical treatment. This report reviews some aspects of the pharmacokinetics of fluoride in man, fluoride bio-availability, plasma kinetics, and kinetics of fluoride in saliva and plaque fluid. Pharmacokinetic studies in growing dogs show that 90% of a single injected fluoride dose is retained shortly after birth, but at maturity it decreases to about 50%. The degree of fluoride accumulating in calcifying tissues seems to be strongly related to age. The bio-availability of fluoride from swallowed fluoride toothpaste is shown to be decreased if the toothpaste is ingested close to a meal. Several studies show that fluoride exerts its cariostatic effects through the liquid phase surrounding the enamel. The importance of fluoride in the fluid environment of the teeth and the kinetics of fluoride in saliva are discussed. Clinical studies using different slow-release fluoride systems indicate that they are promising cariostatic agents–in particular intra-oral slow-release devices and lozenges. A new micro-analytical method to study the kinetics of fluoride in plaque fluid collected from single tooth sites has been developed. Preliminary studies show that the clearance of fluoride from plaque fluid is slowest in the upper incisor region, followed by the molar region, and faster in the lower incisor region. A site-by-site study of the concentration of fluoride in plaque fluid after topical fluoride administration could be extremely beneficial in optimization of the methods and recommended safety regimens for fluoride therapy.