Bone pain palliation is critical for cancer patients afflicted with bone metastases, but radionuclides remain underutilized in such treatments. The authors propose that physician education regarding radionuclide therapy be improved and additional investigations to evaluate newer radionuclides and treatment paradigms (eg, higher activities, repetitive or cyclic administration, chemosensitization, or chemosupplementation) be strongly encouraged. A comprehensive and an interdisciplinary clinical approach toward increasing the use of radionuclides in alleviating metastatic bone pain is proposed. Data from clinical collaborations will help optimize radiopharmaceutical therapy for pain palliation, increase its awareness among oncologists, and contribute effectively to patient palliation and quality-of-life improvements.