The Blood-Retinal Barrier (BRB) is a situation of restricted permeability which is present between the blood and the retina. This barrier has a well defined anatomic substrate, particular permeability characteristics and appears to play a role of major importance in the pathophysiology and therapeutics of retinal disease. The BRB phenomenon operates fundamentally at two levels, retinal vessels and chorioepithelial interface, forming which may be better called an inner BRB and an outer BRB. The main structures involved are, for the inner BRB, the endothelial membrane of the retinal vessels, and for the outer BRB, the retinal pigment epithelium. 'Zonulae occludentes' are present in these membranes forming complete belts around the cells, sealing off the spaces between them. Other structures appear to play an accessory role. Both barriers show an apparent predominance of processes of active transport over mechanisms of passive transfer, these being extremely restricted. Much information on the pathophysiology of the BRB mechanism has been obtained from studies of its experimental breakdown. In this way, a breakdown of the inner BRB may be induced by acute distension of the vessel walls, ischaemia, chemical influences, defects in the endothelial cells and failure of the active transport system, whereas experimental ischaemia, mechanical distension of the pigment epithelial membrane, defects in the pigment epithelium and failure of the active transport systems can cause a breakdown of the outer BRB. The increased permeability of the inner BRB, and of the outer BRB, appears to be related to changes in the vascular endothelial membrane and retinal pigment epithelium, respectively. In clinical ophthalmology there are two methods for the diagnosis of breakdown of the BRB, fundus fluorescein angiography and vitreous fluorophotometry. Vitreous fluorophotometry being capable of detecting functional alterations of the barrier before any pathological changes are apparent. There is evidence of an intimate relationship between breakdown of the BRB and almost every retinal disease, particularly the vascular retinopathies and the pigment epitheliopathies. Diabetic retinopathy, hypertensive retinopathy, retinal vein obstruction, blood diseases, trauma or surgery to the eye, temporary arterial obstruction, perivasculitis, Behçet's and Coats' diseases, retinoblastoma, hemangioblastoma and retinal neovascularization are examples of situations where a breakdown of the inner BRB has been demonstrated. On the other hand, examples of breakdown of the outer BRB include situations of choroidal ischaemia, detachment of the pigment epithelium, choroidal neovascularization, photocoagulation, retinal detachment, Koyanagi's disease, central serous choroidopathy, multifocal inner choroiditis and acute placoid pigment epitheliopathy.