Reduced tissue oxygenation stabilizes the alpha-subunit of the transcription factor hypoxia-inducible factor-1 (HIF-1). This leads to the induction of a number of hypoxia responsive genes. One of the best known HIF-1 targets is erythropoietin that exerts neuroprotective effects on ischemia-related injury in the brain. Thus, pre-exposure to low environmental oxygen concentrations might be exploited as a preconditioning procedure to protect tissues against a variety of harmful conditions. We present recent work on neuroprotection of retinal photoreceptors induced by hypoxic preconditioning or by systemically elevated levels of Epo in mouse plasma.