Cells of Müller glia and microglia react to neuronal injury in glaucoma. The change to a reactive phenotype initiates signaling cascades that may serve a neuroprotective role, but may also proceed to promote damaging effects on retinal neurons. Both effects appear to occur most likely in parallel in glaucoma, but the underlying mechanisms and signaling pathways that specifically promote protective versus destructive roles of reactive glial cells are mostly unclear. More research is needed to understand the homeostatic signaling network in which retinal glia cells are embedded to maintain or restore neuronal function after injury.