Wilms tumor is the most common primary renal malignancy occurring in childhood. Approximately 500 children are diagnosed with Wilms tumor annually in the US alone, most of whom are aged <5 years. Several prognostic factors have been identified, including stage of disease, tumor histology, patient age, tumor weight, and tumor-specific loss of heterozygosity for chromosomes 1p and 16q. During the period from 1969 to 2002, the National Wilms Tumor Study Group coordinated five multicenter Wilms tumor studies. The overall survival rate for Wilms tumor has risen to >90% for patients with tumors of favorable histology. However, the treatment of patients with Wilms tumor with anaplastic histology remains challenging. The optimal treatment strategies for Wilms tumor in relapse will be studied via international collaboration in the near future. Goals of emerging studies include minimizing toxicity while maintaining the outstanding cure rates for patients with a good prognosis and, through advancing biologic understanding and developing novel therapeutic approaches, improving the prognosis for those patients in whom effective cure of their disease continues to elude physicians.