On June 24 the U.S. Food and Drug Administration (FDA) made a major modification to the erythropoiesis stimulating agent (ESA) label, recommending fundamental changes to how ESAs are used to manage chronic kidney disease (CKD) anemia (Table I).1 The FDA emphasized there should be a paradigm shift from aiming for a hemoglobin (Hgb) target range of 10 to 12 g/dL to using the lowest possible dose of ESA to prevent a blood transfusion. Treatment of CKD anemia with ESA therapy should be individualized and, the FDA pointed out, no Hgb target level or ESA dosing strategy should be considered without adverse risk. The FDA has gone further than many would have predicted, but the important issue is how clinicians are going to respond to these label changes in altering their clinical practice. In this article, I will evaluate how these guidelines can be applied to clinical case scenarios that are common in clinical practice. A more detailed discussion of the evidence is published elsewhere.2, 3