Erythropoietin (Epo) has a long-lasting history as the hormon that allows production of red blood cells. It is now well established that, besides erythropoiesis, Epo has the ability to sustain proliferation of myeloid lineages. More recently, extra-haematological roles have been described for Epo. Its receptor, EpoR, has been detected at the membrane of several neoplastic and normal cell types from the central nervous system and other non haematological cell lines. Whereas Epo-EpoR have been detected several years ago in some extra-haematological normal lineages, their role has long been underestimated whereas they may be crucial for proliferation and survival. Consequently, efforts have recently increased to identify the precise role of Epo-EpoR in a variety of cell types. This allowed identification of physiologically relevant targets that led to original therapeutic strategies.