Radiation-induced sarcomas can originate in either the irradiated bone or soft tissues. Most of these tumors are high-grade. The most common histologic subtypes are malignant fibrous histiocytoma (MFH) and osteosarcoma, although other histologies (eg, angiosarcoma, rhabdomyosarcoma) can occur. Tumor size and grade are the two most important prognostic factors for soft tissue sarcomas, including those associated with radiation therapy. The therapy is therefore dictated by the risk of distant metastases. High-grade tumors that are larger than 5 cm should be treated with primary chemotherapy followed by a margin-negative surgical excision of the residual disease. All low-grade tumors and high-grade tumors 5 cm or smaller should be treated with a margin-negative surgical excision, and systemic chemotherapy should be considered when a negative margin is difficult or impossible to accomplish. Radiation-induced sarcomas (either MFH or osteosarcoma) originating in bone should be approached with primary chemotherapy followed by a margin-negative excision similar to de novo bone sarcomas. The dose-intensity of the active agents should be adjusted appropriately for the age, performance status, and prior therapy in a given patient.