Apoptosis of retinal ganglion cells (RGCs) in glaucoma causes progressive visual field loss, making it the primary cause of irreversible blindness worldwide. Elevated intraocular pressure and aging, the main risk factors for glaucoma, accelerate RGC apoptosis. Numerous pathways and mechanisms were found to be involved in RGC death in glaucoma. Neurotrophic factors deprivation is an early event. Oxidative stress, mitochondrial dysfunction, inflammation, glial cell dysfunction, and activation of apoptotic pathways and prosurvival pathways play a significant role in RGC death in glaucoma. The most important among the involved pathways are the MAP-kinase pathway, PI-3 kinase/Akt pathway, Bcl-2 family, caspase family, and IAP family.