The blood-retinal barrier consists of two components which are comprised of the retinal vascular endothelium and the retinal pigment epithelium, respectively. Its functional integrity can be recognized by tight junctions between these cells with a paucity of endocytic vesicles within them and the presence of the molecules that regulate the ionic and metabolic gradients that constitute the barrier. The barrier is compromised in several disease processes and by a variety of agents, but in most cases the location and mechanism for barrier failure is not understood. Perfusion with a variety of radiolabeled tracer molecules, vitreous fluorophotometry, or magnetic resonance imaging can be used to quantitate blood-retinal barrier leakage. Fluorescein angiography or magnetic resonance imaging can localize sites of leakage in vivo with limited resolution. Evans blue dye can be used to visualize blood-retinal barrier failure in gross pathological specimens and immuno-histochemical labeling of serum proteins such as albumin or fibrinogen can be used to localize sites of blood-retinal barrier breakdown by light microscopy. Tracers such as horseradish peroxidase, microperoxidase, or lanthanum, or the immunocytochemical demonstration of albumin can be used to reveal blood-retinal barrier breakdown at the ultrastructural level and provide insights into the mechanisms involved. This review discusses the advantages and limitations of each of these methods to aid in selection of the appropriate techniques to derive the desired information.