Of the approximately 400 children and adolescents diagnosed each year in the United States with rhabdomyosarcoma, between one in five and one in six will be considered high-risk patients by virtue of the presence of one or more sites of distant metastatic disease, most commonly involving lymph nodes, bones, bone marrow, and the lungs. These patients tend to be disproportionately older, of male sex, and have alveolar histology, and most present with bulky tumors (> 5 cm). Typically, though, even in patients with widespread disease, these bulky tumors respond promptly and dramatically to any number of chemotherapy regimens.