Osteosarcoma is the most common malignant bone tumor in children and adolescents. The tumor, which is composed of malignant spindle cells that produce osteoid, typically occurs in the diaphyseal region of long bones; about half of all osteosarcomas arise in the distal femur or proximal tibia. Clinically detectable metastases are present in about 20% of patients at diagnosis, and most patients have subclinical metastases. Effective therapy with complete surgical resection of tumor and intensive multiagent chemotherapy results in the cure of over 50% of patients with osteosarcoma. Recent developments of importance include an improved understanding of the importance of the p53 gene in the pathogenesis of osteosarcoma, the description of preclinical models, the development of improved imaging techniques for determining tumor extent and responsiveness to chemotherapy, and refinements in therapy.