Childhood cancer is the leading cause of death from disease in children between 1 and 15 years of age. Since the introduction of modern multimodality therapy, the prognosis for solid tumors has improved dramatically, with 50% to 60% cure rates. Advances in cytogenetic and molecular genetic techniques are now being used for risk-based treatment in various tumors, including neuroblastoma and rhabdomyosarcoma. Further use of these research tools may lead to a better understanding of oncogenic molecular events, permitting treatment targeted to specific genetic lesions. This article focuses on the clinical features, treatment, and potential future research directions for this diverse group of diseases.