Recognition of the way in which naturally occurring pyrophosphate affects bone metabolism has stimulated the development of a whole series of related compounds, the bisphosphonates. Although the precise mechanism of action of these compounds remains incompletely understood, they have been proven profoundly effective in clinical practice and already constitute a major advance in the therapy of conditions characterised by excessive bone resorption. Serious adverse effects are rare; however, mineralisation problems are a concern, particularly with etidronate. The reduction in bone turnover during prolonged treatment for osteoporosis is also a concern but as yet of uncertain clinical importance. The wide variation in potency of different bisphosphonates in inhibiting the resorption, mineralisation and turnover of bone will increasingly determine which agents are used in various clinical situations. Bisphosphonates are the treatment of choice in Paget's disease and hypercalcaemia of malignancy. They also appear to have potential to alter the course of metastatic bony disease, although the magnitude and clinical importance of any such effect remains unclear. Bisphosphonates show promise in the prevention and treatment of osteoporosis and increase bone mass in postmenopausal and steroid-induced osteoporosis. The effects of these drugs in other situations are less clear and the effects on fracture rates are not yet fully characterised. Optimal regimens have yet to be established but the long half-lives of these agents makes intermittent treatment a rational and convenient approach.