The tight junction or zonula occludens is the most apical structure of the epithelial junctional complex. Tight junctions from semipermeable intercellular diffusion barriers that control paracellular diffusion in a regulated manner. This intercellular junction also acts as an intramembrane fence that prevents the intermixing of apical and basolateral lipids in the exocytoplasmic leaflet of the plasma membrane. Moreover, evidence suggests that tight junction components participate in the regulation of cell growth and differentiation. Occludin was the first identified transmembrane protein of this intercellular junction and received much attention since its molecular characterization. This review discusses experiments that were done with occludin and how they influenced our current thinking of the molecular functioning of tight junctions.