Hypoxic exposure of cells or organisms induces expression of a number of hypoxia responsive genes through the activation of the hypoxia-inducible factor-1 (HIF-1). One of the most prominent HIF-1 targets is erythropoietin that has beneficial effects on ischemia-related injury in the brain. Exposure to low environmental oxygen concentrations can be used as a preconditioning paradigm to protect cells or tissues against a variety of harmful conditions. Here, we summarize recent work on neuroprotection of retinal photoreceptors and ganglion cells induced by hypoxic preconditioning or by systemically elevated levels of Epo in mouse plasma.