Endothelial cells, which are highly dynamic cells essential to the vascular network, play an indispensable role in maintaining the normal function of the body. Several lines of evidence indicate that the phenotype associated with senescent endothelial cells causes or promotes some neurological disorders. In this review, we first discuss the phenotypic changes associated with endothelial cell senescence; subsequently, we provide an overview of the molecular mechanisms of endothelial cell senescence and its relationship with neurological disorders. For refractory neurological diseases such as stroke and atherosclerosis, we intend to provide some valid clues and new directions for clinical treatment options.