The main biologic action of bisphosphonates consists of the inhibition of osteoclastic bone resorption, and, at least, for the drugs introduced after etidronate, without any significant inhibition of bone mineralization. Bisphosphonates therefore play a major role in conditions that are characterized, at least partly, by an increased bone resorption. Primary and secondary osteoporosis by far constitute the most widespread indications for bisphosphonates, mostly because recent published trials have demonstrated their ability to prevent fractures. Potentially crippling conditions such as symptomatic Paget disease of bone remain a major therapeutic challenge for bisphosphonates, but the prevention of the major complications such as sarcoma has still to be proven. The availability of more potent bisphosphonates, less toxic for bones, has certainly widened the therapeutic interventions to asymptomatic patients, bearing in mind the various potential troublesome complications. Fibrous dysplasia resembles, in certain aspects, Paget disease; it is therefore not surprising that bisphosphonate therapy has been proposed in this indication. With the aging of world populations, more and more cancers will be diagnosed. For those with a bone metastatic propensity or malignant hematologic condition, such as multiple myeloma, the most recent generation of more potent bisphosphonates may bring more comfort to crippled patients and even, hopefully, have a direct antitumoral activity, if used synergistically with the armamentarium already available to the clinician. New indications for bisphosphonates include osteogenesis imperfecta both in children and adults. In the future, they might be used in the prevention of erosions in rheumatoid arthritis and of loosening of joint prostheses, as well as possibly in osteoarthritis. Now that the fear of theoretically freezing bone remodeling has been reasonably dismissed, potential uses for bisphosphonates might be considered nearly infinite.