In prostate cancer, the development of skeletal metastases is associated with a significant increase in morbidity, mainly because of severe bone pain, which eventually becomes refractory to conventional analgesia. Androgen ablation is the treatment of choice, but the majority of patients relapse within 2 to 3 years from initiation of treatment. After failure of hormone therapy, external-beam irradiation therapy is effective in the palliation of pain, but radionuclides represent an attractive and cost-effective alternative. Strontium 89 is currently the most commonly used radionuclide in the palliative management of prostate cancer metastatic to the skeleton. The rationale for the use of bisphosphonates in metastatic prostate cancer is not immediately obvious, given the predominantly osteoblastic nature of the metastatic process. The clinical use of these agents rests on a number of basic and clinical observations that provide ample evidence that, in prostate cancer, the metastatic process is associated with increased bone resorption. Evidence regarding the beneficial effects of bisphosphonates in reducing morbidity from metastatic prostate cancer is reasonably solid, although the choice of optimal bisphosphonate, mode of administration, dose, and duration of treatment must be determined in large, controlled studies before their widespread clinical use can be advocated. Available therapeutic modalities that use either radionuclides or bisphosphonates can effectively and safely be used in the palliative management of metastatic prostate cancer. Neither radionuclides nor bisphosphonates have been shown to prolong survival, but the potential of both agents to beneficially alter the metastatic process in prostate cancer is intriguing.