Curative treatment for high-grade osteosarcoma consists in surgery of the primary tumor and chemotherapy, in order to achieve a limb salvage surgery and increase the disease-free survival rate. Patients with suggestive diagnosis of osteosarcoma should be sent to a reference center before biopsy. Confirmation of diagnosis by a pathologist with particular expertise in bone tumors is recommended. Multimodal treatment is often given within the framework of prospective collaborative studies. Currently, doxorubicin, cisplatinum, high-dose methotrexate and ifosfamide are considered the most active agents against osteosarcoma. High-dose methotrexate with leucovorin rescue always takes part of first-line regimen in children and adolescents, alternative regimens are proposed for adults because of excessive toxicity despite appropriate management by skilled teams. Compared with surgery alone, multimodal treatment of localized high-grade osteosarcoma improves outcome for patients from 20% to more than 60% of them been alive 5-year after diagnosis.