Endothelial cells and astrocytes are the two main types of cells in the blood–brain barrier, and each plays a pivotal role in the central nervous system. Although they have different functional characteristics, they can mutually communicate and cooperate with each other to maintain the normal function of the neurovascular unit and are substantially altered during pathology. Understanding the relationship between astrocytes and endothelial cells can lay the foundation for advancing protective therapies against central nervous system diseases. From a new perspective of the interactions between endothelial cells and astrocytes, this paper presents a summary of the interaction modes of the two cells and the current research status in the central nervous system and further elucidates the function and mechanism of the interactions between the two cells in various central nervous system diseases. The aim of this study is to provide a theoretical foundation for further understanding the mechanism of action of these two kinds of cells in central nervous system diseases and provide new ideas for the treatment of related diseases.