Cerebrovascular disease (CVD) is a significant neurological condition resulting from pathological changes in the brain's blood supply and is currently the leading cause of death and disability worldwide. The progression of CVD is closely associated with endothelial damage, plaque formation, and thrombosis, driven by long-term alterations in vascular endothelial cells, smooth muscle cells, microglia, and other immune-inflammatory cells. Among the key molecular pathways involved, the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway plays a central role. Dysregulation of the JAK-STAT pathway is implicated in the pathogenesis of CVD by influencing the aforementioned cell types and associated pathological processes. Importantly, the role of the JAK-STAT pathway varies across different types of CVD and throughout different stages of disease progression (e.g., pre-morbid, acute, and chronic phases). This review examines the composition, activation, and regulation of the JAK-STAT pathway and summarizes recent findings on its involvement in CVD. We discuss the distinct roles of JAK-STAT signaling in various CVD conditions, the potential reasons for these differences, and explore the clinical translational prospects and technical challenges of targeting the JAK-STAT pathway for therapeutic intervention in CVD.