The transmembrane chemokines CX3CL1 and CXCL16 mediate chemotaxis and cell to cell adhesion by interaction with their receptors CXCR6 and CX3CR1, respectively. We here summarize reports on the expression, regulation and proteolytic processing of transmembrane chemokines by glial cells, their activity on glial cells/glial precursor cells and their role in glial cell cross-talk under physiological and pathophysiological conditions.