Glaucoma is a group of diseases characterized by progressive optic nerve degeneration, with the characteristic pathological change being death of retinal ganglion cells (RGCs), which ultimately causes visual field loss and irreversible blindness. Elevated intraocular pressure (IOP) remains the most important risk factor for glaucoma, but the exact mechanism responsible for the death of RGCs is currently unknown. Neurotrophic factor deficiency, impaired mitochondrial structure and function, disrupted axonal transport, disturbed Ca2+ homeostasis, and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma. This review was conducted using Web of Science, PubMed, Project, and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma, in addition to outlining protective treatments to improve the degradation of RGCs.