In order to carry out their physiological functions, the cells of transporting epithelial tissues must be able to polarize their cell surface domains. Different collections of membrane transport proteins must be distributed to distinct domains of the plasma membrane, and cells must be coupled to one-another through junctional complexes that help organize polarized domains and regulate the permeability of the paracellular pathway. This exquisite organization requires that epithelial cells possess a sorting apparatus that can target newly synthesized transport proteins to the appropriate surface domains. Furthermore, the transport proteins themselves must possess information embedded within their structures that specifies their sites of ultimate functional residence. The nature of this information, and of the protein-protein interactions involved in its interpretation, is beginning to be elucidated. The initial formation of the polarized state involves signaling cascades that epithelial cells use to orient themselves to sites of cell-cell and cell-matrix contact. Recent evidence suggests that one component of these cascades is a kinase that also serves as a cellular energy sensor.