In response to optic nerve damage, astrocytes become reactive. This reactivity can be identified by the presence of morphological and molecular changes throughout the retina and optic nerve as well as the formation of a glial scar. The process of astrocyte activation exhibits spatial and temporal characteristics, and it is finely regulated by complex signaling mechanisms. Excessive astrocyte activation plays a crucial role in progressive optic nerve injury. This review focuses on the spatial and temporal characteristics and mechanisms of astrocyte activation and discusses the modulation of astrocyte activation. Further insight into astrocyte activation might provide targets for future therapeutic interventions. © 2014 Wiley Periodicals, Inc.