The polarized insertion of membrane proteins in epithelial cells is a highly regulated process that involves the coordinated interaction of many subsets of intracellular proteins. Thus, like cog-wheels in a complex machine, the different parts of the trafficking pathway must work together to ensure the correct functioning of an individual cell and of the entire epithelium in which it resides. The individual portions of the trafficking pathway include (1) sorting of membrane proteins into the correct apically or basolaterally targeted vesicles at the level of the trans-Golgi network; (2) delivery of these vesicles to their correct membrane destination by the microtubular (and probably the actin) cytoskeleton; (3) fusion of the vesicles with the appropriate membrane domain via a complex set of fusion proteins. This review has briefly outlined some of these processes and has used examples from the kidney to illustrate their importance to normal renal function.