This review focuses on the interaction of fluoride with the material properties of bone and teeth, which is of clinical, scientific, and public health interest. These tissues are composed primarily of collagen (protein) and hydroxyapatite (mineral), and their mechanical function depends on the properties of the constituents, their proportions, the interface, and the three-dimensional structure. Changing any of these may have clinical consequences. Fluoride interacts with mineralized tissues in a number of ways. At low doses, the fluoride may be passively incorporated into the mineral, stabilizing it against dissolution; this is one of the mechanisms by which municipally fluoridated water reduces the incidence of dental caries. At higher doses, such as those used for treatment of osteoporosis, the fluoride may alter the amount and structure of tissue present, including altering the interface between the collagen and mineral. At very high doses, skeletal and dental fluorosis occurs, characterized by debilitating changes in the skeleton and by marked mottling and discoloration of teeth, which may be accompanied by increased wear of the enamel. These effects have been observed in communities where the local drinking water has naturally high fluoride levels. Understanding the influence of fluoride on mineralized tissues is, therefore, of considerable significance.