Pain palliation with bone-seeking radiopharmaceuticals is an effective and cost-effective management tool in patients with advanced cancer metastatic to bone. Strontium-89 ((89)Sr) (Metastron) and samarium-153 ((153)Sm) EDTMP (Lexidronam) are licensed for use in patients in the United States. Patients with a positive bone scan using technetium 99m methylene diphosphonate ((99m)Tc MDP) are eligible for treatment, and indications and contraindications for use are now well defined. The evidence in the literature now suggests that the radiopharmaceuticals can significantly reduce pain and analgesic requirements, can improve quality of life, can reduce lifetime radiotherapy requirements and management costs, and may slow the progression of painful metastatic lesions. Retreatment is safe and effective. Rhenium-186 ((186)Re) HEDP and Tin-117m diethylenetriaminepenta-acetic acid (DTPA) are in phase II/III trials to evaluate efficacy and compare efficacy with the licensed agents. Phosphorus-32 ((32)P) has been reassessed in two trials evaluating efficacy in comparison with (89)Sr and safety. Toxicity is reversible myelosuppression, which may be significant, and the treatments should not be given to patients with suspected disseminated intravascular coagulation.