Although the concept of a humoral regulator of erythropoiesis was introduced more than 100 years ago, its existence was first firmly established a little more than 50 years ago. This review briefly describes the historical development of information about erythropoietin. It then describes our current understanding of where erythropoietin is produced; the factors that regulate its rate of production; how erythropoietin acts at the cellular level to stimulate erythropoiesis; and its role in the regulation of the rate of erythropoiesis. Finally, it discusses the clinical uses of erythropoietin in the diagnosis and therapy of hematopoietic diseases.