Ewing sarcoma family of tumors (ESFTs) includes extraosseous ES, adult neuroblastoma, Askin's tumor, paravertebral small-cell tumor, and atypical ES. ESFTs affects young people between ages 10 and 20 years and can develop in almost any bone or soft tissue but is most common in the flat and long flat bones. Classically, ES showed evidence of bony destruction and its soft tissue component is homogeneous on computed tomography. The classic cytogenetic abnormality associated with this disease is a reciprocal translocation of the long arms of chromosomes 11 and 22, t (11; 22). VEGF and PDGF are important regulators of angiogenesis in ESFT. The role of c-KIT (tyrosine kinase) expression in ES is being determined. Patients with ES or another of the ESFT require referral to centers that have multidisciplinary teams of sarcoma specialists. With rare exception, systemic combination chemotherapy and definitive local therapy is required in all patients, and care should be coordinated among the medical oncologist, surgeon, and radiation therapist.