Multiple cellular components, including neuronal, glial and endothelial cells, are involved in the sophisticated pathological processes following central nervous system injury. The pathological process cannot reduce damage or improve functional recovery by merely targeting the molecular mechanisms of neuronal cell death after central nerve system injuries. Eph receptors and ephrin ligands have drawn wide attention since the discovery of their extensive distribution and unique bidirectional signaling between astrocytes and neurons. The roles of Eph/ephrin bidirectional signaling in the developmental processes have been reported in previous research. Recent observations suggest that Eph/ephrin bidirectional signaling continues to be expressed in most regions and cell types in the adult central nervous system, playing diverse roles. The Eph/ephrin complex mediates neurogenesis and angiogenesis, promotes glial scar formation, regulates endocrine levels, inhibits myelin formation and aggravates inflammation and nerve pain caused by injury. The interaction between Eph and ephrin is also considered to be the key to angiogenesis. This review focuses on the roles of Eph/ephrin bidirectional signaling in the repair of central nervous system injuries.