Doctors who treat patients with osteoporosis are increasingly confronted with the question of how long to continue treatment with bisphosphonates (BPs), which have the unique characteristic of accumulating in the skeleton. Limited available long-term data suggest that such decisions should be made on a case-by-case approach and guided by an individual re-evaluation of clinical fracture risks and bone mineral density, efficacy, and safety issues. In patients who still have a high fracture risk after 5 years of treatment with BPs, continuing treatment could be considered, but stopping BPs could be appropriate in those with a low fracture risk after 5 years of treatment. Switching to recombinant human parathyroid hormone 1-34 or 1-84 is indicated when recurrent incident vertebral fractures occur despite adequate antiresorptive therapy for more than 1 year. However, the usefulness of more than 5 years of treatment with BPs needs to be proved with higher levels of evidence-based medicine.