The brain contains glial cells (astrocytes, microglia, and oligodendrocytes) and endothelial cells in addition to neurons. Under various pathologic conditions, the invasion of leukocytes such as neutrophils, monocytes/macrophages, and lymphocytes is observed. Interactions among these cell types play crucial roles both in brain function and dysfunction. However, the molecular basis of such interactions remains unclear. Cytokines and chemokines were originally identified as essential mediators of inflammatory and immune responses. Enhanced production and release of cytokines/chemokines are observed also in the central nervous system under various pathologic conditions. There is growing evidence showing that brain cytokines/chemokines play crucial roles in the neuro-glio-vascular interaction underlying the pathology of various brain disorders and therefore are potential targets for the development of novel and effective therapeutics for central nervous system diseases. This article reviews the evidence for the involvement of cytokines/chemokines in ischemic brain injury and presents our data on introducing organotypic brain slice cultures and in vitro blood brain barrier models as useful tools to investigate neuro-glio-vascular interaction.