Purpose of the Review <p>Osteoporosis requires life-long management. This involves the use of different drugs in various sequences followed by long-term maintenance therapy. This review highlights the important transitions among osteoporosis therapies and outlines a strategy of intermittent bisphosphonate therapy for long-term maintenance.</p> Recent Findings <p>Over the past few years, the effects and limitations of long-term treatment with bisphosphonates and denosumab have become apparent as have several key factors in the sequential use of anti-remodeling drugs and osteoanabolic agents. Strategies for transitions from estrogen, bisphosphonates, denosumab and the bone-forming drugs will be discussed, based on extant evidence, clinical experience and expert opinion.</p> Summary <p>By appropriate selection of both the initial and subsequent drugs for the prevention and treatment of osteoporosis, therapeutic benefits can be optimized and safety issues minimized. Developing a strategy for long-term maintenance of the benefits of the initial therapies can provide a life plan for managing patients with osteoporosis.</p>