Morphological studies demonstrating the presence in the retinal vessels of 'zonulae occludente' between the endothelial cells and physiological studies examining diffusion gradients in the vitreous after systemic or intravitreal administration of fluorescein, performed under the guidance of David Maurice, established the basis of the Blood-Retinal Barrier (BRB) concept. The BRB system is briefly reviewed as well as its role in health and disease. Regulation of the microenvironment of the retina is fundamental for appropriate retinal function and vision. The diffusional characteristics and transport functions of the BRB system may be evaluated and followed by vitreous fluorometry. Its clinical use has shown the importance of BRB alterations in a variety of retinal diseases but has been restricted by the lack of disease specificity. A recent development, the Retinal Leakage Analyzer, maps BRB alterations and has opened new perspectives for multimodal macula mapping and improved evaluation of newly available drugs that show promise for stabilizing the BRB.