This paper reviews the contribution of chemotherapy in the conquest of osteosarcoma. It discusses how the treatment of osteosarcoma has evolved over the last five decades, resulting in a more than fivefold increase in survival. Though the initial improvements in survival were dramatic, essentially there has been no change in the outlook for this disease over the past 30 years. The paper also highlights the necessity of a multidisciplinary approach to combat this disease and stresses the need to explore newer treatment agents in order to build on the lessons learnt from the past while striving to achieve greater levels of success. 1. Introduction Bone cancers are rare in humans. In 2009, it is estimated that 2570 new cases of bone sarcomas were diagnosed in the United States [1]. Osteosarcoma is the most common. The term “osteosarcoma” as opposed to “osteogenic sarcoma” is preferred by the World Health Organization (WHO). The eponym was introduced by Boyer in 1805 [2]. In 1879, Gross published a paper entitled “Sarcoma of the Long Bone Based upon a Study of One Hundred and Sixty-five Cases” [3]. Most, if not all the tumors, were probably osteosarcoma. He advocated treatment by early amputation. The outcome was dismal; nonetheless it was accepted as the “standard” of treatment. In the course of the ensuing one and a half century, osteosarcoma became established as a distinct pathological and radiological entity with no change in the “standard” of therapy. The survival rate was less than 10%; in rare publications, it occasionally rose to 20%. The dismal survival was due to the biological behavior of the malignancy: pulmonary micrometastases were present in at least 80% of patients at diagnosis. These metastases were not visible on conventional imaging studies. However, they surfaced 8–12 months after amputation and were responsible for the patient’s demise within 12 to 24 months of their appearance. Osteosarcoma therefore had to be considered a systemic disease with systemic therapy required for cure. Until the mid-20th century, no such therapy was available. 2. Radiation Therapy In view of the poor prognosis with primary surgical ablation, Sir Stanford Cade a British Surgeon Radiotherapist in 1931 advocated radiation therapy to treat the primary tumor [4]. Following completion of therapy (6000？rad over six weeks) the patient was observed for the possible emergence of pulmonary metastases for 6–9 months; if metastases failed to appear, an elective amputation was performed. The intent was to avoid “futile mutilation” in a patient destined to die. It was
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