Formation and maintenance of the blood-retinal barrier is required for proper vision and loss of this barrier contributes to the pathology of a wide number of retinal diseases. The retina is responsible for converting visible light into the electrochemical signal interpreted by the brain as vision. Multiple cell types are required for this function, which are organized into eight distinct cell layers. These neural and glial cells gain metabolic support from a unique vascular structure that provides the necessary nutrients while minimizing interference with light sensing. In addition to the vascular contribution, the retina also possesses an epithelial barrier, the retinal pigment epithelium, which is located at the posterior of the eye and controls exchange of nutrients with the choroidal vessels. Together the vascular and epithelial components of the blood-retinal barrier maintain the specialized environment of the neural retina. Both the vascular endothelium and pigment epithelium possess a well-developed junctional complex that includes both adherens and tight junctions conferring a high degree of control of solute and fluid permeability. Understanding induction and regulation of the blood-retinal barrier will allow the development of therapies aimed at restoring the barrier when compromised in disease or allowing the specific transport of therapies across this barrier when needed. This chapter will highlight the anatomical structure of the blood-retinal barrier and explore the molecular structure of the tight junctions that provide the unique barrier properties of the blood--retinal barrier.