The neurovascular unit (NVU), consisting of endothelial cells, basement membrane, pericytes, astrocytes and microglial cells, couples local neuronal function to local cerebral blood flow and regulates transport of blood-borne molecules across the blood-brain barrier (BBB). The building blocks and the phenotype of the NVU are well-established but the intercellular signaling between the different components remains elusive. A better understanding of the cellular interactions and signaling within the NVU is critical for the development of efficient therapeutics for the treatment of a variety of brain diseases, such as brain cancer, stroke, neuroinflammation and neurodegeneration. This review gives an overview about the current in vivo knowledge of the NVU and the communication between its different cellular constituents. We also discuss the usefulness of various model organisms for studies of the brain vasculature.