The epithelial tight junction (TJ) is responsible for the control of paracellular transport between epithelial cells (gate function) and the maintenance of apical/basolateral polarity by preventing the diffusion of membrane lipids and/or proteins from one surface domain to another (fence function). Renal tubule epithelia in the mammalian nephron have TJs that determine paracellular transport characteristics. Paracellular transport across renal tubular epithelial TJs (gate function) varies in different segments of the nephron. A large family of recently identified TJ-associated transmembrane proteins named claudins appear to determine the paracellular permeability properties of the TJ. A combination of inherited human diseases, renal epithelial cell culture models, and nephron expression patterns of claudins is providing important clues about how claudin molecules determine the TJ gate function of renal epithelia in different segments of the nephron.