The current treatments of and new therapeutic options for the management of Ewing's sarcoma (ES) are reviewed.ES is the second most common primary bone malignancy in pediatric patients and is numbered among the cancers that result in the greatest risk of mortality and morbidity in children and young adults. Much progress has been made in the treatment of ES since the disease was first described in the 1920s. With current multimodality treatment including chemotherapy, radiation, and surgery, patients with localized disease have a long-term survival rate of approximately 50%. Survival rates for patients with metastatic disease or those with early relapse remain poor. New combinations of cytotoxic agents such as cyclophosphamide, topotecan, irinotecan, and temozolomide have shown efficacy and tolerability in patients with relapsed or refractory disease. To date, the role of high-dose chemotherapy supported by stem cell rescue as a consolidation therapy for high-risk ES tumors has yet to be conclusively determined. Much effort is being invested in treating cancer with targeted therapies, and the EWS-ETS fusion gene would likely provide an important tumor-specific target. Tyrosine kinases (TKs) are overexpressed in human sarcoma tumors, and cell lines may serve as potential targets for new therapies. One TK receptor that is a promising therapeutic target is insulinlike growth factor-1 receptor.Treatments for ES include surgery, radiation, and cytotoxic regimens, many of which include vincristine. Treatment for recurrent ES has included topotecan, cyclophosphamide, temozolomide, and irinotecan. Angiogenesis inhibitors, TK inhibitors, and bisphosphonates have also been studied.