Bisphosphonates have unique pharmacological characteristics unlike those of any other drug group. Millions of adults take oral bisphosphonates for long-term treatment of osteoporosis and osteopenia; some of these people will most likely also seek orthodontic treatment. Adverse dental effects from bisphosphonates have been reported, including decreased tooth movement, impaired bone healing, and osteonecrosis in the mandible and the maxilla. Osteonecrosis has been rarely observed after bisphosphonate use for osteoporosis. However, adverse drug effects might occur more frequently in orthodontic patients, and they would probably be noted before the end-stage pathology of osteonecrosis. Adverse effects during orthodontic treatment, including decreased tooth movement, could last for years after the drug therapy is stopped. Successful orthodontic treatment requires optimal bone healing to prevent excessive tooth mobility. Bisphosphonates appear to have 2 bone elimination rates--a fast elimination of weeks from the bone surface and a slow elimination of years after incorporation into the bone structure. This article presents methods to clinically and radiographically monitor orthodontic patients who are taking oral bisphosphonates. Efforts to minimize adverse effects and optimize orthodontic procedures with physician-approved drug holidays are discussed. The orthodontic treatment results of 3 patients who received bisphosphonate therapy are reported.