Abstract: The cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway has emerged as a key mediator of neuroinflammation. While current studies primarily attribute its effects to neurons and glial cells, emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature, particularly in brain endothelial cells. Therefore, studying the role of inflammation caused by the cGAS– STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions. Here, we review the multifaceted role of global cGAS–STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS– STING in brain endothelial cells.