Increasing age is an adverse prognostic factor in the treatment of primary bone tumors. There are few published data on treatment of primary bone tumors in adults. This paper presents data from the Department of Sarcoma Medical Oncology at The University of Texas MD Anderson Cancer Center, summarizing our treatment results. To treat primary osteosarcoma, we used 90 mg/m2 of doxorubicin as a continuous intravenous infusion over 48 to 96 hours and 120 to 160 mg/m2 of cisplatin intravenously or intra-arterially. Initially, we found a marked difference in postoperative continuous disease-free survival (CDFS) between those with 90% or greater (i.e., good response) tumor necrosis and those with less than 90% (i.e., poor response) tumor necrosis. The sequential addition of high-dose methotrexate and ifosfamide to patients with poorly responding disease improved their CDFS to that of patients with good response. Older patients and those who have tumors with variant histology have inferior outcomes. Evaluation of subsequent patients revealed similar outcomes for those with good or poor response to induction therapy, supporting our practice of adaptation of postoperative chemotherapy to the results of preoperative chemotherapy. PET-CT is the best imaging modality to screen for a response with tumors inside bone. To treat Ewing sarcoma, we have employed 2 mg of vincristine, 75 to 90 mg/m2 of doxorubicin as a 72-hour infusion, and 2.5 g/m2 of ifosfamide over 3 hours daily for 4 doses (i.e., vincristine, doxorubicin, and ifosfamide [VAI]). Preliminary analysis indicates a higher CDFS when adjusted for patient age than seen with the standard alternating regimen used in pediatrics. A screening MRI of the pelvis and spine can detect subtle metastatic disease in bone or bone marrow that is missed by other imaging modalities or blind biopsy. Chondrosarcoma is treated surgically or on investigational protocols. Giant cell tumor of bone is usually managed surgically, but multiple options exist for medical treatment, and therapy is individualized with embolization, denosumab, and interferon.