Glaucoma is recognized to have its major detrimental effect upon the eye by killing retinal ganglion cells. The process of cell death appears to be initiated at the optic nerve head, though other sites of injury are possible but unsubstantiated. At present the injury at the nerve head seems related to the level of the eye pressure, but its detailed mechanism is as yet unexplained. There is a greater loss of ganglion cells from some areas of the eye, and this feature of glaucoma seems related to the regional structure of the supporting connective tissues of the optic nerve head. Larger retinal ganglion cells have been consistently shown to have somewhat greater susceptibility to injury in glaucoma, though all cells are injured, even early in the process. Ganglion cells die by apoptosis in human and experimental glaucoma, opening several potential areas for future therapies to protect them from dying. Neurotrophin deprivation is one possible cause of cell death and replacement therapy is a potential approach to treatment.