Management of renal anemia in the large and at-risk population of non-dialysis chronic kidney disease (CKD) patients is a critical issue. In particular, definition of the optimal hemoglobin (Hb) target for therapy is controversial but highly warranted by physicians and patients worldwide. Recently, international clinical practice guidelines have recommended delayed initiation of erythropoiesis-stimulating agents (ESA) and lower Hb target levels during maintenance therapy. However, geographical differences in terms of ESA dose needed to achieve a given Hb value can be evidenced, with US patients showing higher prevalence of ESA resistance. On the other hand, non-US patients are often maintained in a higher Hb range by means of low ESA doses. This critical point has never been addressed. Nevertheless, outside of the US, translating the restrictive recommendations of new guidelines, which are essentially based on trials in US patients, can lead to negative effects, such as an increased need for a blood transfusion, and worsening of quality of life. In this article we provide a reappraisal of current recommendations on anemia management in non-dialysis CKD in light of the geographical differences in individual responsiveness to ESA.