Fluorosis occurs when fluoride interacts with mineralizing tissues, causing alterations in the mineralization process. In dental enamel, fluorosis causes subsurface hypomineralizations or porosity, which extend toward the dentinal-enamel junction as severity increases. This subsurface porosity is most likely caused by a delay in the hydrolysis and removal of enamel proteins, particularly amelogenins, as the enamel matures. This delay could be due to the direct effect of fluoride on the ameloblasts or to an interaction of fluoride with the proteins or proteinases in the mineralizing matrix. The specific mechanisms by which fluoride causes the changes leading to enamel fluorosis are not well defined; though the early-maturation stage of enamel formation appears to be particularly sensitive to fluoride exposure. The development of fluorosis is highly dependent on the dose, duration, and timing of fluoride exposure. The risk of enamel fluorosis is lowest when exposure takes place only during the secretory stage, but highest when exposure occurs in both secretory and maturation stages. The incidence of dental fluorosis is best correlated with the total cumulative fluoride exposure to the developing dentition. Fluoride supplements can contribute to the total fluoride exposure of children, and if the total fluoride exposure to the developing teeth is excessive, fluorosis will result.