Small blood vessels express specific phenotypical and functional characteristics throughout the body. Alterations in the microcirculation contribute to many correlated physiological and pathological events in related organs. Factors such as comorbidities and genetics contribute to the complexity of this topic. Small vessel disease primarily affects end organs that receive significant cardiac output, such as the brain, kidney, and retina. Despite the differences in location, concurrent changes are seen in the micro-vasculature of the brain, retina, and kidneys under pathological conditions due to their common histological, functional, and embryological characteristics. While the cardiovascular basis of pathology in association with the brain, retina, or kidneys has been well documented, this is a simple review that uniquely considers the relationship between all three organs and highlights the prevalence of coexisting end organ injuries in an attempt to elucidate connections between the brain, retina, and kidneys, which has the potential to transform diagnostic and therapeutic approaches.