The outer blood-retinal barrier is formed by the retinal pigment epithelium. In any epithelial monolayer, the tight junctions enable the epithelium to form a barrier by joining neighboring cells together and regulating transepithelial diffusion through the paracellular spaces. Tight junctions are complex, dynamic structures that regulate cell proliferation, polarity, and paracellular diffusion. The specific properties of tight junctions vary among epithelia, according to the physiological role of the epithelium. Unlike other epithelia, the apical surface of the retinal pigment epithelium interacts with a solid tissue, the neural retina. Secretions of the developing neural retina regulate the assembly, maturation, and tissue-specific properties of these tight junctions. The slow time course of development allows investigators to dissect the mechanisms of junction assembly and function. These studies are aided by culture systems that model different stages of development.