Osteoporosis is a common condition that leads to substantial morbidity and mortality and affects an increasing number of persons worldwide. Several pharmacological therapies that inhibit bone resorption, promote bone formation, or both, are available for the treatment of osteoporosis. The osteoanabolic treatment spectrum was recently expanded by the introduction of a novel bone-forming agent in the United States, and clinical trials indicate that a new class of bone anabolic therapy may become available. Both antiresorptive and bone anabolic therapies are associated with common and rare adverse effects, which are particularly important to address as these drugs are used for long-term treatment in numerous patients with a large proportion being elderly and/or having multimorbidity. In addition, antiresorptive drugs are used to inhibit bone resorption in patients with malignant hypercalcaemia or to prevent skeletal events in cancer patients, and bisphosphonates have been repurposed as a cancer preventive therapy. However, therapeutic doses are generally higher when antiresorptive drugs are used in the oncological setting, which influence the prevalence of adverse effects significantly. This review highlights key issues and controversies regarding adverse effects of currently available and emerging drugs used for osteoporosis and metastatic bone diseases.