In the haematopoietic system, the principal function of erythropoietin (EPO) is the regulation of RBC production. Consequently, following the cloning of the EPO gene, recombinant human EPO (rHuEPO) forms have been widely used for treatment of anaemia in chronic kidney disease and chemotherapy-induced anaemia in cancer patients. However, a steadily growing body of evidence indicates that the therapeutic benefits of rHuEPO could be far beyond the correction of anaemia. Several articles have been recently published on the tissue-protective, nonhaematological effects of rHuEPO that prevent ischaemia-induced tissue damage in several organs including the kidney.In this review, we focus on nonhaematological effects of rHuEPO in various experimental settings of acute and chronic kidney injury. Because this tissue-protective action of rHuEPO is not the result of correction of anaemia-related tissue hypoxia, we will also discuss potential molecular pathways involved. Finally, we will review the current literature on clinical studies with rHuEPO or analogous substances and progression of chronic kidney disease, and propose possible clinical renoprotective strategies.