Systemic targeted radionuclide therapy is a method of delivering radiation specifically to the surface of tumor cells or to the local microenvironment, largely bypassing most normal tissues, and resulting in a continuous bombardment of malignant cells as the radionuclide decays. Several agents are currently approved in the United States, both for the treatment of low-grade lymphomas and for painful osteoblastic bone metastases. Their clinical adoption has been somewhat limited over the years, due to a number of factors: a lack of radiation oncologists as authorized users; a disinterest of nuclear medicine physicians; an irrational fear and misunderstanding of the agents by referring medical oncologists; financial concerns; politics; and a false perception that providing these treatments would be complicated, expensive, and an undue regulatory burden for participating radiation oncologists. However, recently, a number of novel radiopharmaceutical agents have shown promising clinical outcomes for patients with few effective therapies, including an alpha-emitter that extends overall survival in patients with metastatic prostate cancer. For this reason, there is renewed enthusiasm in the oncology community for access to these therapeutic radiopharmaceuticals. Radiation oncologists, as authorized users for these agents, will be seen as the natural leaders in providing access to these therapeutic agents. It is critical that ASTRO provide education to its members regarding the growing importance of these agents and to demystify the process we navigate in order to bring these tools into our own practices. At the conclusion of this activity, the learner will be able to do the following: 1. Explain systemic use of alpha emitters, an area of radiotherapy that is new to most practitioners. 2. Identify the therapeutic and safety differences between alpha- and beta-emitting radioisotopes. 3. Discuss the process of establishing a radiopharmaceutical program in the learner's own practice.