Primary bone cancers are rare neoplasms, with osteosarcoma, chondrosarcoma, and Ewing's sarcoma the 3 most common forms. Chondrosarcoma is usually found in middle-aged and older adults. Wide excision is the preferred treatment for resectable low- and high-grade chondrosarcomas. Intralesional excision with or without adjuvant therapy is an alternative option for low-grade lesions. In small series of reports, the addition of chemotherapy improved outcomes in patients with mesenchymal chondrosarcomas. However, the role of chemotherapy in the treatment of chondrosarcomas is not yet defined. Ewing's sarcoma is characterized by a chromosomal translocation t(11;22), resulting in the fusion of EWS gene with various members of the ETS family of genes, and develops mainly in children and young adults. Multiagent chemotherapy is the primary treatment for patients with Ewing's sarcoma. Patients who experience response to primary treatment are treated with local control therapy (surgery or radiation) followed by adjuvant chemotherapy. Progressive disease is best managed with RT with or without surgery followed by chemotherapy or best supportive care. Osteosarcoma occurs mainly in children and young adults. Wide excision is the primary treatment for patients with low-grade osteosarcomas, whereas preoperative chemotherapy is preferred before wide excision for high-grade osteosarcoma and periosteal lesions. After wide excision (for resectable lesions), postoperative chemotherapy is recommended for patients with low-grade or periosteal sarcomas with pathologic findings of high-grade disease and those with high-grade sarcoma. RT followed by adjuvant chemotherapy is recommended if the sarcoma remains unresectable after preoperative chemotherapy. Patients with relapsed or refractory disease should be treated with second-line therapy. Participation in a clinical trial should be strongly encouraged for patients experiencing progressive disease after second-line therapy. The development of multiagent chemotherapy regimens for neoadjuvant and adjuvant treatment has considerably improved the prognosis for patients with osteosarcoma and Ewing's sarcoma. A small subset of patients diagnosed with metastatic disease at presentation can be cured with the proper treatment. Consistent with the NCCN philosophy, the panel encourages patients to participate in well-designed clinical trials to enable further advances. © Journal of the National Comprehensive Cancer Network.