Bisphosphonates are widely used in the treatment of osteoporosis in postmenopausal women and older men. In clinical trials they have been shown to reduce fractures in women with osteoporosis and there is increasing evidence that they are also effective in women with osteopenia, in whom the majority of fractures occur. In addition to their role as initial therapy in individuals at increased risk of fracture, bisphosphonates are used as sequential therapy after treatment with anabolic drugs. There are no head-to head studies to compare the anti-fracture efficacy of different bisphosphonates, but there is limited evidence that zoledronate treatment results in greater increases in BMD than risedronate or alendronate. This, together with the need for less frequent administration of zoledronate, supports its wider use in clinical practice, particularly if longer dosing intervals than those currently recommended are shown to be effective.