Recent cell biologic studies of protein trafficking, sorting, and distribution in polarized renal epithelial cells have begun to provide important new insights into the mechanisms involved in generating and maintaining cell surface polarity. Advances in this field have been rapid in the last year, due in part to the development of new approaches to analyzing protein delivery and distribution in polarized renal cells grown in vitro. Sorting signals within apical and basal-lateral membrane proteins have been described that may be involved in the segregation of proteins into different populations of transport vesicles in the trans-Golgi network; the nature of these signals has provided insight into the mechanisms involved. Elements of the cytoskeleton appear to be involved in the delivery of these transport vesicles to the appropriate membrane domain (microtubules) and in the retention of specific proteins in the correct membrane domain (membrane skeleton). Finally, detailed analysis of two prominent renal diseases, ischemia and polycystic kidney disease, indicates that abnormalities in the regulation of membrane protein distribution may be a contributing factor in generating the disease state.