This review is about vascular endothelial phenotype heterogeneity in the retinal and choroidal circulations. It is becoming increasingly clear that the functional and structural heterogeneity is present in the retinal and choroidal circulations. Differential responses of the vessels to vasoactive substances have been shown with intraluminal and extraluminal delivery and in different regions of the same vascular bed. Vascular endothelial phenotype is highly heterogenic and site-specific, particularly in the retinal and choroidal veins. Updated information of such heterogeneity may help us to further understand the control mechanisms of the retinal and choroidal circulations which are important in compensating for the physiological and pathological challenges faced by these vascular beds. The site-specific changes of vascular endothelial phenotype may be linked with endothelium dysfunction, and site-specific diseases such as central and branch retinal vein occlusion. Endothelial dysfunction has been recognized as an initial step for many vascular diseases. Endothelial cells are a strategic and valid target for therapeutic intervention. Fundamentally important questions regarding the role of vascular endothelial cell function in the eye are discussed.