Osteosarcoma (OS) remains the most common primary malignant bone cancer affecting children and adolescents. Majority of patients are subjected to surgery and chemotherapy with limited alternatives to consider. However, with increasing knowledge of the molecular pathogenesis of OS, advancements in OS therapy research fields have developed potential agents for a more targeted and localised approach to treatment. Thus, this review attempts to examine some common treatment strategies (surgery, radiotherapy and chemotherapy) employed clinically as well as recent developments in newer experimental therapy methods (gene therapy) which might potentially benefit patients.