Primary malignant bone tumors in the pediatric to young adult populations are relatively uncommon and account for about 6 % of all cancers in those less than 20 years old [1] and 3 % of all cancers in adolescents and young adults (AYA) within the age range of 15 to 29 years [2]. Osteosarcoma (OS) and Ewing's sarcoma (ES) comprise the majority of malignant bone tumors. The approach to treatment for both tumors consists of local control measures (surgery or radiation) as well as systemic therapy with high-dose chemotherapy. Despite earlier advances, there have been no substantial improvements in outcomes over the past several decades, particularly for patients with metastatic disease. This review summarizes the major advances in the treatment of OS and ES and the standard therapies available today, current active clinical trials, and areas of investigation into molecularly targeted therapies.