The study of Wilms tumor has provided a model for the evaluation of the histopathology, prognostic factors, and multimodality therapy regimens in children and adults with rare malignant tumors. The NWTS Group has provided the scientific and administrative framework for the assessment of various treatment schemes in children with renal tumors, a research goal that could not have been realized using the resources available to either a single or a small group of institutions. These studies have yielded higher survival rates while demonstrating that therapy can be individualized according to well-defined risk factors most accurately identified in non-pretreated tumors. Thus, it has been found that treatments associated with significant acute and/or long-term morbidity are not necessary for patients with stage I or II, favorable histology Wilms tumor. Future studies may allow more accurate identification of those patients with stage III and IV/favorable histology Wilms tumor for whom treatment with an anthracycline is not necessary. If successful, this would decrease the size of the group of survivors at risk for cardiac dysfunction, which can follow the administration of even modest cumulative dosages of these agents.