Glaucoma, a leading cause of irreversible blindness globally, primarily affects retinal ganglion cells (RGCs). This review dives into the anatomy of RGC subtypes, covering the different underlying theoretical mechanisms that lead to RGC susceptibility in glaucoma, including mechanical, vascular, excitotoxicity, and neurotrophic factor deficiency, as well as oxidative stress and inflammation. Furthermore, we examined numerous imaging methods and functional assessments to gain insight into RGC health. Finally, we investigated the current possible neuroprotective targets for RGCs that could help with future glaucoma research and management.