In many diseases associated with deterioration of the visual field and eyesight, optic nerve ganglion cells are at the highest risk. The clinical course of primary chronic open-angle glaucoma (PCOAG) is also determined by the degree of damage to these cells. Due to their anatomy, they are subject to extreme stress exerted by metabolic and microcirculatory forces. The interaction between hypoxia and metabolic stress leads to damage of the retinal ganglion cells. This is compounded by oxidative stress and age-dependent increase of advanced glycation end products. The following contribution gives consideration to approaches for delaying ganglion cell death in PCOAG, e.g., with neuroprotective agents. Furthermore, agents that reduce calcium influx into the cells could prevent cell destruction. Likewise, NMDA receptor antagonists could be effective; however, considerable side effects are to be feared. Antioxidants are also attributed with theoretical impact in combating PCOAG by preventing apoptosis. Finally, the ideal glaucoma medication should be well tolerated when taken orally, prevent destruction of retinal ganglion cells, and possess a low side effect profile.