Although advances have been made in both surgical and medical management of patients with osteosarcoma, the overall survival of patients with osteosarcoma has remained constant, with no substantial improvement in the past 15 years. Advances in imaging have had a substantial impact on surgical planning and staging. These advances have, in turn, had a major impact on the surgeon’s ability to perform limb-sparing surgery. Surgical techniques have improved in terms of instrumentation, modularity of implants and availability. Limb salvage has proven to be an acceptable method of treatment both with respect to oncologic and functional outcome in those patients where a wide resection may be achieved. The use of massive allografts has been largely replaced with the use of modern oncologic endoprostheses. Biologic targets that will enable new therapies to have maximum effect on tumor cells while minimizing toxicity to the host tissues need to be identified.