Osteosarcoma, the most common bone sarcoma, affects approximately 560 children and adolescents annually in the United States. The incidence of new diagnoses peaks in the second decade of life. Twenty percent of patients present with clinically detectable metastases, with micrometastases presumed to be present in many of the remaining patients. Treatment typically includes preoperative chemotherapy, surgical resection, and postoperative chemotherapy. Limb-salvage procedures with wide surgical margins are the mainstay of surgical intervention. Advances in chemotherapy protocols have led to a 5-year survival rate of 60% to 78%. Among the goals of future treatment regimens are improved chemotherapeutic agents with higher specificity and lower toxicity.