Various theories exist to explain how glaucoma is initiated to result in the differential rate of retinal ganglion cell death. We suggest that initially the quality of the blood supply in the optic nerve head region is affected to cause a type of ischemia. This causes an alteration in ganglion cell mitochondrial homeostasis and an activation of astrocytes and other glia in the optic nerve head. Thereafter, as the disease progresses substances released from activated glial cells and also blue light reaching the retina act synergistically to cause the death of specific ganglion cells at different times. We therefore propose that the repertoire of receptors and number of mitochondria in individual ganglion cells relate to their time of death after glaucoma is initiated. These ideas will be presented, as they suggest that the causes and mechanisms for individual ganglion cells dying in glaucoma vary. Such a theory implies that substances with a single mode of action is unlikely to be sufficient for effective clinical neuroprotection but that this might be achievable using substances with multiple modes of action or a suitable cocktail mixture of products.