The bisphosphonates have revolutionized the therapy of osteoporosis, particularly the prevention of vertebral and hip fractures. The development of tools for defining absolute fracture risk facilitates their targeting to appropriate, at-risk individuals. Prescribers need to be aware of their common side effects (gastrointestinal intolerance with oral dosing and flu-like illness following intravenous use). Whether these agents carry a real risk of other problems such as osteonecrosis of the jaw and subtrochanteric fractures remains uncertain at the present time. If the association of these problems with bisphosphonates is real, it is important that the major therapeutic benefits that can accrue from bisphosphonates' appropriate targeted use are not lost as a result of the anxiety concerning these extremely rare adverse events.