The intestinal barrier plays a critical role in humans in the transport of nutrients and macromolecules. At the same time, it has to provide an effective barrier to harmful macromolecules and microorganisms. The tight junction (TJ) is an essential component of this barrier. The junctional complexes of the plasma membrane are not simply epithelial barriers in paracellular transport or barriers preventing diffusion in the plasma membrane, but also contain proteins involved in signal transduction and the maintenance of the physiological epithelial cell state. Occludin, claudin, junctional adhesion molecules, and the coxsackie virus and adenovirus receptor are the major components of TJs. This article highlights the structure and function of TJs as well as the molecular interactions occurring during permeation through TJs.