Osteoporosis has become a major public health concern worldwide. Significant morbidity, mortality, and health expenditures are associated with osteoporotic fractures. Evidence from randomized controlled trials and meta- analyses supports the efficacy and safety of oral bisphosphonates as first-line pharmacologic agents for the prevention and treatment of osteoporosis. This article reviews the evidence demonstrating the beneficial effects of etidronate, alendronate, and risedronate on improving bone mass and preventing fractures in individuals with or at risk for osteoporosis. Issues surrounding dosing intervals and optimal duration of therapy are also discussed. We conclude that the nitrogen-containing bisphosphonates alendronate and risedronate are safe and efficacious agents in preventing and treating osteoporosis. They are superior to cyclical etidronate in improving appendicular bone mass, and in reducing future risk for nonvertebral fractures. Once-weekly dosing options with alendronate and risedronate are effective and reduce serious adverse drug effects, and therefore, are welcome additions to our therapeutic armamentarium.