Neuroblastoma is an enigmatic tumor that has the highest rate of spontaneous regression of all human malignant neoplasms, yet has one of the poorest outcomes when occurring as disseminated disease in children. The emergence of neuroblastoma tumor biology, coupled with age and stage of diagnosis, has allowed more accurate routing of patients to risk-related therapy and refining of such therapy to minimize treatment for those with low risk for recurrent disease and searching out new treatment strategies for patients with high-risk disease. Continued assessment of tumor biologic features in all patients will provide new insights into tumorigenesis, cell differentiation, and death pathways, resulting in the potential for developing newer therapies for patients with high-risk disease.