The benign mesenchymal diseases, for which radiation is often quite effective in halting progression or achieving complete and permanent resolution, include neoplastic and nonneoplastic processes (eg, giant cell tumor of bone to keloid). Radiation oncologists have been reluctant to employ radiation in the management of patients with benign disease for several reasons: (1) the small but nonzero risk of late appearance of radiation-induced malignant tumors; (2) were radiation subsequently required to be employed in the same region of the body for treatment of a separate and independent neoplasm, the radiation dose might have to be reduced to an ineffective level; and (3) nonmalignant tissue changes that might appear at quite remote times and complicate healing of surgical wounds. Currently a liberalization of the use of radiation is in progress because of the clinical seriousness of many benign processes for which radiation yields a major therapeutic benefit. This reassessment of radiation oncology in the United States has been stimulated by the much wider application of radiation for patients with a wide spectrum of benign diseases in several European countries. This article considers the major indications and the expected outcomes from radiation treatment of benign mesenchymal diseases. For benign neoplasms that are locally progressive, the radiation dose is usually in the range 50 to 60 Gy administered at 1.8 to 2.0 Gy/fraction, five fractions per week. The response is characteristically quite slow, and the long-term local control probability is high (80%). Further, the response probability is not sensitive to lesion size, in contrast to malignant tumors of the mesenchymal tissues. For the nonneoplastic processes managed in some instances by radiation, the doses recommended are usually in the range of 6 to 12 Gy as single-dose or 20 to 25 Gy as fractionated dose irradiation. The efficacy of such treatment tends to be equal to or less than that noted for the benign neoplastic diseases.