Musculoskeletal oncology encompasses a broad array of diseases and treatment challenges. The most important issue facing a patient with a sarcoma is cure. Traditional cytotoxic chemotherapy has evolved empirically over the last several decades. While substantial improvements have been made in cure rates for pediatric patients with sarcoma, cure rates have plateaued at considerably less than 100% and chemotherapy for adult patients is far less effective. Starting with cytogenetic analysis and, more recently, the molecular dissection of tumors, it has become obvious that "sarcoma" is not a diagnosis per se but a group of diseases. Adult soft-tissue sarcoma alone comprises many different histologic subtypes. A better understanding of the biology of tumors at the molecular level has brought forth the possibility of targeted therapy, prompting the American Academy of Orthopaedic Surgeons (AAOS) and the Orthopaedic Research Society (ORS) to hold the Molecular Biology and Therapeutics in Musculoskeletal Oncology Research Symposium in September 2008.