Radiotherapy is a valuable treatment option for a variety of nonmalignant diseases. As the indications for low-dose radiotherapy to benign conditions evolve, it is prudent to consider risks and how these might weigh against the benefits of therapy. Radiation-induced malignancies are one consideration and are more likely associated with higher doses of radiation and genetic cancer susceptibility. Radiotherapy for nonmalignant diseases typically involves doses much lower than those associated with radiation-induced malignancies. In addition, treatments are employed for conditions that are more common in the older patient population, whereas much of the historical experience with radiation-induced malignancies involves children and young adults. The low doses associated with radiotherapy for nonmalignant diseases and the patient population in whom these treatments are employed makes the estimated risk of radiation-induced carcinogenesis low. Specific factors that increase the concern for radiation-induced malignancies include repeated radiotherapy to the same site, leading to cumulative increasing dosage, radiotherapy in younger individuals, and those with known germline mutations in DNA repair genes.