Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from numerous placebo-controlled trials demonstrating efficacy in fracture risk reduction over 3-5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about adverse effects related to long-term use. For most patients with osteoporosis, the benefits of treatment outweigh the risks. Because these agents accumulate in bone with some persistent antifracture efficacy after therapy is stopped, it is reasonable to consider a 'drug holiday.' There is considerable controversy regarding the optimal duration of therapy and the length of the holiday, both of which should be based on individual assessments of risk and benefit.