Osteosarcoma is the most common type of bone cancer in children and young adults with a peak incidence in adolescents. It has a propensity for lung metastases and is a prime example of a cancer where cure will only be achieved if many specialities closely cooperate within a dedicated multidisciplinary environment. Neither surgery nor chemotherapy alone will cure many patients, but their combination can lead to long-term, disease-free survival in 60–70%. Primary tumor surgery should aim for wide resection margins. These can often be achieved by limb-salvage surgery rather than amputation. If staging detects primary metastases, these must also be resected. Radiotherapy has very limited indications. Chemotherapy is usually started preoperatively. A combination of high-dose methotrexate with folinic acid (leucovorin) rescue, adriamycin (doxorubicin), and cisplatin (MAP) is often considered a standard, but other regimens, often incorporating ifosfamide, can achieve similar results. Other agents have not been universally accepted. Poor prognostic factors include large primary tumors, presence of metastases, and a poor histologic response to preoperative chemotherapy. Efforts to reduce the recurrence risk of patients with poorly responding osteosarcomas by postoperative chemotherapy modifications have been unsuccessful. Surgery is the mainstay of treatment at recurrence; the contribution of second line systemic treatments is far less well defined. Unfortunately, survival rates both in North America and in Europe have improved little over several decades. It is hoped that a more profound knowledge of the biological characteristics of this rare cancer will lead to novel treatment approaches which will finally overcome this stagnation.