Accumulating evidence has revealed that the tyrosine kinases play a major role in glioma proliferation and invasion. The largest family of tyrosine kinases, the Eph family, and its ligands, the ephrins, are frequently overexpressed in glioma, suggesting important roles for their bidirectional signals in glioma pathobiology. Ephs bind to cell surface-associated ephrin ligands on neighboring cells and have many biological functions during embryonic development of the central nervous system, including axon mapping, cell migration, and angiogenesis. Recent findings suggest that Eph/ephrin signaling affects glioma cell growth, migration, and invasion in vitro and in vivo. However, their roles in glioma seem complex, because both tumor growth promoter and suppressor potentials have been ascribed to Ephs and ephrins. Here, we review recent advances in research on the role of Eph/ephrin signaling in glioma and suggest that the Eph/ephrin system could be a potential target of glioma therapy.