Glaucoma is a chronic neurodegenerative disease of the optic nerve, in which apoptosis of retinal ganglion cells (RGCs) and progressive loss of optic nerve axons result in structural and functional deficits in glaucoma patients. This neurodegenerative disease is indeed a leading cause of blindness in the world. The glaucomatous neurodegenerative environment has been associated with the activation of multiple pathogenic mechanisms for RGC death and axon degeneration. Growing evidence obtained from clinical and experimental studies over the last decade also strongly suggests the involvement of the immune system in this neurodegenerative process. Paradoxically, the roles of the immune system in glaucoma have been described as either neuroprotective or neurodestructive. A balance between beneficial immunity and harmful autoimmune neurodegeneration may ultimately determine the fate of RGCs in response to various stressors in glaucomatous eyes. Based on clinical data in humans, it has been proposed that one form of glaucoma may be an autoimmune neuropathy, in which an individual's immune response facilitates a somatic and/or axonal degeneration of RGCs by the very system which normally serves to protect it against tissue stress.