The prognosis for high-risk Ewing's tumors has been improved by multimodal radiation and chemotherapy. Ewing's family of tumors requires risk-adapted treatment. Risk stratification is dependent on stage, tumor localization and volume, and the pattern of disease spread at the time of diagnosis and the time of relapse. The concepts for high-dose therapy followed by hematopoietic cell transplantation in Ewing's family of tumors are based on dose-response and dose-intensity relationships. This article will discuss the use of high-dose therapy followed by hematopoietic cell transplantation, focusing on recent progress with respect to agent combinations, dose and outcomes of therapy.