Over the past 30 years, a significant improvement in the prognosis of localized osteosarcoma of the extremities has been observed. Despite these results, approximately 30-40% of patients will relapse, mostly within the first 3 years from diagnosis. The prognosis of patients with recurrent disease or metastases at diagnosis is poor. To improve the survival in this patient population, several attempts have been made. An increased dose intensity of chemotherapy induces short lasting remission but does not increase the survival. In the era of targeted therapy, few drugs have been tested with dismal results. The use of biological agents endowed with immunomodulant activity (that is IL-2) or reduced-intensity allogeneic hemopoietic SCT has produced intriguing results that need further confirmation. In this context, an ongoing study explores the antitumor activity of specific T-cytotoxic lymphocytes.