Osteoporosis is a chronic disease, and antiresorptive treatments are often continued for many years. Despite their established efficacy in reducing fracture risk, the most commonly used antiresorptive treatments, bisphosphonates and denosumab, have short- and long-term risks that, coupled with their benefits and other unique characteristics, influence consideration for at least periodic discontinuation. Bisphosphonates retain their effects even after discontinuation due to their prolonged skeletal retention, whereas denosumab discontinuation is associated with a rapid rebound in bone turnover and increased fracture risk. There is controversy about how, when, and why to potentially stop these agents. We discuss both permanent and temporary discontinuation of long-term treatment with bisphosphonates and denosumab. We focus on the reasons and timing for discontinuation as well as strategies to mitigate future fracture risk.