Background: Local control of osteosarcoma is difficult in cases for whom surgery might yield unacceptable functional outcomes. We evaluated the efficacy of radiotherapy and gemcitabine and docetaxel chemotherapy (GEMDOC) in this setting. Methods: Data of 9 patients (5 male, 4 female) who received radiotherapy and GEMDOC chemotherapy at Korea Cancer Center Hospital were retrospectively reviewed. Tumor response was evaluated according to dimensional (Response Evaluation Criteria in Solid Tumors, version 1.1) or metabolic changes using 18F-fluorodeoxy-D-glucose (FDG)-PET. Results: The median age of the patients was 14.7 years (range, 12.6 – 21.1 years). Patients received a median 4 courses of GEMDOC chemotherapy (range, 2 − 6 courses). Five patients received radiotherapy at the bone (4 with multiple metastatic bone lesions, 1 with refractory sacral tumor) and 3 cases at the lungs. One patient received radiotherapy for microscopically residual tumor at the shoulder. The median dose of radiotherapy was 42 Gy (range, 22 – 60 Gy). Eight cases were eligible for response evaluation; there were 1 complete response (CR, metabolic CR) and 2 partial responses ( PR, including 1 metabolic PR). The response was maintained for 6.1 months in 2 cases and 4.6 months in 1 patient. Myelosuppression was the most frequent toxicity (5 patients), and grade 3 palmar plantar erythrodysesthesia was observed in 2 cases. Patients were followed for a median of 7.1 months (range, 2.7 – 13.4 months) and the median progression-free survival after this treatment was 2.0 months (range, 1.1 – 6.1 months). At the time of this analysis, 1 patient is alive with disease, 2 are lost to follow-up and 6 died of disease. Conclusion: Radiotherapy with GEMDOC chemotherapy showed some activity in cases with refractory tumor or with multiple metastasis. Further studies are needed to investigate the efficacy of newer radiotherapy modalities (e.g., proton-based radiotherapy), as well as to identify new radiosensitizing chemotherapy regimens.