The blood-retina barrier (BRB) is composed of both an inner and an outer barrier. The outer BRB refers to the barrier formed at the retinal pigment epithelial (RPE) cell layer and functions, in part, to regulate the movement of solutes and nutrients from the choroid to the sub-retinal space. In contrast, the inner BRB, similar to the blood brain barrier (BBB) is located in the inner retinal microvasculature and comprises the microvascular endothelium which line these vessels. The tight junctions located between these cells mediate highly selective diffusion of molecules from the blood to the retina and the barrier is essential in maintaining retinal homeostasis. In this chapter, we summarize the key differences between the iBRB and oBRB and outline the molecular constituents of the tight junctions associated with the iBRB. We also describe a process for modulation of the iBRB to enhance systemic delivery of therapeutics to the retina, a technology which may pave the way for safer and more effective therapies for retinal diseases. Pubmed