Wilms' tumor or nephroblastoma is the most frequent renal tumor in children and is associated with different congenital anomalies and syndromes. A significant number of studies in genetics and molecular biology have improved our understanding of this malignancy discovering as well how different genes play a critical role in the organogenesis process. Derived from these studies promising markers have emerged relating translational medicine with clinical prognosis, which has been traditionally defined by the histopathological changes and the tumoral stage. During the last 40 years the therapeutic outcomes have improved after multi-centric and multidisciplinary efforts represented mainly by The National Wilms' Tumor Study Group (currently the Renal Tumor Committee of the Children's Oncology Group) from North America and the International Society of Paediatric Oncology from Europe and this has served as a role model for establishing similar trials for other pediatric tumors. Our aim with this chapter of Wilms' tumor is to present the state of knowledge in translational and clinical areas in a balanced perspective.