There are important similarities in molecular composition and structural organization of the interface between the vitreous and retina and that between the retina and retinal pigment epithelium. It is striking that the two most common causes of severe vision loss in the western world involve neovascularization at these interfaces; i.e., proliferative diabetic vitreo-retinopathy at the vitreo-retinal interface and exudative age-related macular degeneration at the retina-retinal pigment epithelium interface. Improved knowledge of the physiology of these interfaces will lead to a better understanding of the effects of aging and diseases, especially those that involve neovascularization. Such advances will no doubt result in new treatment strategies offering more effective therapy, and, even more importantly, perhaps providing prevention from these devastating causes of blindness.