Ectopia of the initial ureter is the first ontogenic mis-step that leads to many congenital anomalies of the kidney and urinary tract (CAKUT). The ectopia results in hypoplastic kidney, ectopia of the ureteral orifice, urinary outflow obstruction and/or reflux. Recent studies on several mutant mouse models verified that ectopic ureteral budding indeed occurs prior to the formation of CAKUT. Often, the genes involved in navigating the site of ureteral budding also regulate later ontogenic processes of the kidney and other urinary tract systems. These additional functions of the genes underlie the wide spectrum of CAKUT, as the genes are expressed at multiple sites at multiple ontogenic stages, and regulate the morphogenesis of the many portions of the excretory system through their distinctive cellular functions.