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Over the past years, knowledge has expanded with regards to the multiple roles played by erythropoietin (EPO) in the body. Once believed to be a hormone synthesised in the kidney and involved only in the modulation of erythrocyte production, it is recognised now that EPO can be produced in many tissues, including the retina, and by many cells. In these tissues EPO is released in response to “tissue injury” and appears to have protective functions. Despite the extensive research conducted to date, the cues leading to release of EPO and its effects in the normal and diseased retina have not been fully elucidated.In vitro and in vivo experimental studies as well as small interventional clinical studies suggest a potential beneficial effect of externally administered EPO in early diabetic retinopathy and diabetic macular oedema. In contrast, controversy exists with regards to the possible use of EPO in proliferative diabetic retinopathy. Non-erythropoietic EPO-derived peptides, produced with the aim of increasing effectiveness and reducing side effects of EPO, are currently under investigation in early phase clinical trials.