It has been known for many years that the epithelia of the urogenital system derive from mesenchyme. Essential regulators of this conversion have recently been discovered, and cellular changes have been described. However, we do not have a coherent view of how these dramatic changes are integrated, nor do we know the source or identity of extracellular signals that must regulate epithelialization of mesenchymal precursors. The metanephric kidney, Wolffian duct, and the Drosophila midgut are the leading model systems to describe how epithelia derive from mesenchyme.