The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Studies demonstrate changes of autoantibody concentrations against retinal and optic nerve head antigens in glaucoma patients. Furthermore we found antibody deposits in human glaucomatous retinae in a pro-inflammatory environment. Clinical studies showed up regulated, but also significantly down-regulated autoantibody levels. These antibodies belong to the natural autoimmunity. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also neuroprotective characteristics and influence the protein expression of neuroretinal cells. A misbalance in the physiological equilibrium may shift from regulatory immunity into a neuroinflammatory degenerative process, what may lead to a predisposition to glaucoma. However, the protective nature of autoantibodies and the molecular mechanisms underlying the very sensitive equilibrium of natural autoimmunity between autoaggression and neuroprotection offer promising target sites for new therapeutic approaches. Finally, the changes in antibody profiles represent a new opportunity as highly sensitive and specific biomarkers for diagnostics purposes.