Osteosarcoma is the most common bone tumor in children, adolescents, and young adults. Before 1970, treatment relied mainly on surgery, but the introduction of chemotherapy significantly improved survival rates. The most effective chemotherapy regimen is high-dose methotrexate, doxorubicin, and cisplatin (MAP). Despite extensive research, the survival rate has not improved significantly, and new agents like muramyl tripeptide and ifosfamide have not shown clear benefits. Collaborative efforts are essential to improve outcomes through preclinical models and clinical trials. International collaboration has led to the development of standardized treatment protocols and improved survival rates. The EURAMOS study demonstrated that histologic response is a prognostic factor but should not guide postoperative treatment decisions. Current research focuses on understanding the biology of osteosarcoma and developing new therapies. The TARGET program is investigating the genomic basis of osteosarcoma to identify potential therapeutic targets. New agents like eribulin, denosumab, and glembatumumab vedotin are being tested in clinical trials. Continued international collaboration is crucial for advancing treatment and improving survival for patients with osteosarcoma.Osteosarcoma is the most common bone tumor in children, adolescents, and young adults. Before 1970, treatment relied mainly on surgery, but the introduction of chemotherapy significantly improved survival rates. The most effective chemotherapy regimen is high-dose methotrexate, doxorubicin, and cisplatin (MAP). Despite extensive research, the survival rate has not improved significantly, and new agents like muramyl tripeptide and ifosfamide have not shown clear benefits. Collaborative efforts are essential to improve outcomes through preclinical models and clinical trials. International collaboration has led to the development of standardized treatment protocols and improved survival rates. The EURAMOS study demonstrated that histologic response is a prognostic factor but should not guide postoperative treatment decisions. Current research focuses on understanding the biology of osteosarcoma and developing new therapies. The TARGET program is investigating the genomic basis of osteosarcoma to identify potential therapeutic targets. New agents like eribulin, denosumab, and glembatumumab vedotin are being tested in clinical trials. Continued international collaboration is crucial for advancing treatment and improving survival for patients with osteosarcoma.