Bisphosphonates, which are potent bone resorption inhibitors, currently are the mainstay of treatment for osteoporosis. Antifracture efficacy has been demonstrated for at least three nitrogen-containing bisphosphonates in oral formulations that are designed to be administered in weekly or monthly dosing regimens. Frequent reports of adverse events, primarily related to the upper gastrointestinal tract, and the strict dosing schedule necessary for oral bisphosphonate therapy are considered the major reasons for disappointing adherence to therapy. New intravenous formulations have been developed that allow dosing at very long intervals, thus avoiding the gastrointestinal complications associated with oral bisphosphonates and, it is hoped, improving compliance, particularly for patients who are intolerant of oral bisphosphonates or have contraindications to their use. This alternative approach holds promise for improved outcomes of osteoporosis treatment and ultimately for reduced health care costs related to caring for people with fragility fractures.