Wilms tumor (WT) is an embryonal renal neoplasm that has proven to be an exceptionally productive model for the study of tumor pathogenesis and therapy. It also provides a striking demonstration of what can be achieved through the collaborative study of rare tumors, as well as the importance of incorporating formal pathological review into the design of therapeutic cancer trials. As a result of the National Wilms Tumor Study, a majority of children are now cured of their WT with less intense and prolonged therapy than was customary at the middle of the 20th century. The presence of extreme polyploidy (anaplasia) identifies a small subset of WT which have a grim prognosis in the context of present therapy, and which will require innovative therapeutic intensification. Recent evidence suggests that anaplasia is a marker of resistance to adjuvant therapy, rather than increased aggressiveness. Stage I anaplastic WT and advanced-stage WT with anaplasia limited to a portion of the primary tumor seem to fare as well as nonanaplastic WT and do not require therapeutic intensification. New neoplastic entities formerly confused with WT have been identified, and refinements of staging criteria have been achieved. New insight into the pathogenesis has significant implications for clinical management. Despite these achievements, much remains to be learned from this tumor model, before we have achieved the ultimate goal of curing every child with WT, while exposing that child to the minimum possible adverse sequelae of therapy. Adverse effects of therapy are far more significant for the young child cured of cancer than for the elderly patient, and their avoidance is therefore the most important goal beyond the cure itself.