Abstract: Calcium (Ca2+) is a key intracellular messenger involved in a variety of cellular functions. Intracellular Ca2+ dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions. Retinal ganglion cell (RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies. Ca2+ function in RGCs has been primarily studied regarding its association with neuronal activity. However, the role of RGC Ca2+ homeostasis and its dysregulation following degeneration is less clear. Here, we describe recent findings using rodent models of RGC degeneration that suggest a role for Ca2+ homeostasis in RGC loss and neuroprotection.