The molecular genetic characterization of Wilms' tumor has played a prominent role in advancing our knowledge of the genetic aspects underlying the development of cancer in general. Unlike the genetic mechanism leading to the development of retinoblastoma, an embryonal tumor of childhood affecting the retina, which only requires the inactivation of one single gene, the biological pathways leading to the development of Wilms' tumor are complex and likely involve several genetic loci. These include two genes on chromosome 11p; one on chromosome 11p13 (the Wilms' tumor suppressor gene WT1) and the other on chromosome 11p15 (the putative Wilms' tumor suppressor gene WT2). In addition to these two genes, loci at 1p, 7p, 16q, 17p (the p53 tumor suppressor gene), and 19q (the putative familial Wilms' tumor gene FWT2) are also believed to harbor genes involved in the biology of Wilms' tumor. Herein these loci are reviewed and their clinical significance is summarized.