The American Journal of Neuroradiology has played a seminal role in the history of vertebral augmentation (VA). Because VA is increasingly being included in the multidisciplinary management of malignant vertebral compression fractures (VCFs), combined therapeutic approaches that include strategies to treat metastatic disease along with the fracture have become appealing options for patients. To that end, we recently investigated the dosimetric feasibility of treating malignant VCFs with radionuclide therapy. The goal would be to provide local control of the systemic disease beyond the pain relief and structural support provided by polymethylmethacrylate cement. The purpose of this article is to propose a methodology for evaluating radionuclides for use in radiation therapy that takes into account a number of factors including radiation characteristics, biochemical effects, production capacity, and safety. The goal of such a methodology is to introduce a systematic approach to selecting radionuclides in designing treatment regimens and future investigations and also to stimulate discussion and experimentation involving new radionuclides that may provide more effective treatments than the current isotopes in widespread use.