Bisphosphonates now occupy a prominent position among therapeutic options for the prevention and treatment of various forms of osteoporosis. Their clinical profile of bone-specific efficacy, rapid response, protection from both spine and hip fractures in patients with osteoporosis, and excellent tolerability is all that can be expected of an anti-remodeling drug. Even in the era of anabolic agents, bisphosphonates will continue to be important treatment options. It is not possible to compare or contrast the clinical effectiveness of the various bisphosphonates on the basis of existing data. Despite marked differences in the in vitro potency of drugs, the clinical responses to each of the bisphosphonates discussed above are similar. New bisphosphonates may not be more effective but will provide different tolerability profiles and different routes of administration, thereby increasing the number of patients in whom bisphosphonates can be used. Having these effective agents challenges clinicians to identify the most appropriate patients for bisphosphonate use and to develop strategies to improve acceptance of and adherence to these useful agents.