Optic neuropathy refers to dysfunction and/or degeneration of axons of the optic nerve with subsequent optic nerve atrophy. A common feature of different optic neuropathies is retinal ganglion cell (RGC) apoptosis and axonal damage. Glaucoma and optic neuritis are the two major degenerative causes of optic nerve damage. Here, we review the anatomy and pathology of the optic nerve, and etiological categories of optic neuropathies, and discuss rodent models that can mimic these conditions. Electrophysiology can reveal signature features of RGC damage using the pattern electroretinogram (PERG), scotopic threshold response (STR) and photopic negative response (PhNR). The amplitude of the visual evoked potential (VEP) also reflects RGC axonal damage. The neurotrophin-mediated survival pathways, as well as the extrinsic and intrinsic cell apoptotic pathways, play a critical role in the pathogenesis of RGC loss. Finally, promising neuroprotective approaches based on the molecular signaling are analyzed for the treatment of optic neuropathies.