Wilms tumor is the most common renal malignancy that occurs in childhood. The remarkable evolution of treatment for this malignancy has served as a paradigm for multimodal cancer treatment. A rich database has accrued over time from well-controlled clinical trials. Translational research has directly affected patient care by allowing risk-based therapy. This article will summarize advances in our knowledge of the biology of Wilms tumor and describe the impact on clinical treatment of Wilms tumor.