Erythropoietin is the major glycoprotein hormone regulator of mammalian erythropoiesis. Erythropoietin is secreted by the kidney in response to decreased blood oxygen. It circulates in the blood, and binds and activates a specific receptor expressed on bone marrow erythroblasts. The erythropoietin receptor is a member of the cytokine receptor superfamily. Considerable details now exist to explain the biochemical events that follow erythropoietin receptor activation. Moreover, the erythropoietin receptor has been shown to play a role in the pathogenesis of various human disease including erythroleukemia and familial erythrocytosis. This review describes the structure of the cell surface erythropoietin receptor and the nature of its biochemical responses.