Fluoride has often been used as a treatment for osteoporosis, a metabolic bone disease of considerable importance in the elderly population. The techniques currently used to monitor a patient's response to fluoride are outlined. New findings concerning (1) a mechanism for interaction of fluoride with osteoblasts (via mitogenic signals or growth factors); (2) toxicity and carcinogenesis; (3) recent clinical trial data; and (4) the importance of dosage, administration regimens, and side effects in an effective fluoride treatment protocol are reviewed. Some recent clinical data challenge the efficacy of fluoride in the treatment of postmenopausal osteoporosis. Because of the implications of these recent studies with respect to fracture incidence during fluoride therapy, fluoride cannot be recommended at this time for general use in the treatment of osteoporosis.