Several mechanisms have been postulated to explain the optic nerve damage that occurs in primary open angle glaucoma (POAG). No single mechanism can adequately explain the great variations in susceptibility to damage and the patterns of damage seen in this syndrome. The etiology of POAG is likely to be multifactorial. Mechanical, vascular and other factors may influence individual susceptibility to optic nerve damage. An enhanced understanding of the nature of the optic nerve damage in POAG and improved methods of study may result in earlier diagnosis or may allow us to distinguish among different pathological processes all currently grouped under the diagnosis of POAG. As we gain a better understanding of the neuropharmacology and cellular biology of injury and repair of the visual system we will undoubtedly refine the concepts of glaucomatous optic neuropathy.