Kautz et al. recently identified a new hormone, erythroferrone (ERFE), that mediates hepcidin suppression during stress erythropoiesis. ERFE is produced by erythroblasts in response to erythropoietin. ERFE-deficient mice fail to suppress hepcidin rapidly after hemorrhage and exhibit a delay in recovery from blood loss. ERFE expression is greatly increased in Hbbth3/+ mice with thalassemia intermedia, in which it contributes to the suppression of hepcidin and the systemic iron overload characteristic of this disease. The cartoon (Figure) shows the suggested mechanism of action of ERFE. If the contribution of ERFE to hepcidin suppression and iron overload in iron-loading anemias is confirmed in clinical studies, ERFE neutralization would be a rational and apparently specific therapeutic strategy. At the other end of the disease spectrum, the ability of ERFE to suppress hepcidin expression could be useful in treating iron-restrictive anemias characterized by increased hepcidin, including anemia of inflammation and anemia of chronic kidney disease.