Coronary microcirculatory dysfunction (CMD) is a major cause of myocardial ischemia that influences the outcomes of patients with coronary artery disease. The mechanisms of CMD are heterogeneous and may result from a spectrum of biological and cardiovascular risk factors that may affect also the microcirculation of other vital organs. Microcirculatory dysfunction of the brain, known as cerebral small vessel disease, is increasingly being recognized as a cause of cognitive decline and neurodegenerative disorders. Despite microvascular dysfunction of the heart and the brain may share underlying pathophysiological mechanisms (endothelial dysfunction, thrombosis, vascular remodeling and capillary rarefaction), the evidence about the potential link between both pathological processes is scarce. In this paper we discuss the mechanisms of microvascular dysfunction of the heart and the brain, their clinical impact on cardiac events, cognitive decline and neurodegenerative disorders, and the potential link between both vascular target organs at the level of the microcirculation.