Optimal treatment algorithms for erythropoiesis-stimulating agent (ESA) and iron therapy in anemic CKD patients are lacking. Kuragano et al. evaluated hemodialysis patients over two years and report increased mortality risk and/or adverse events in those with high serum ferritin levels and high ferritin fluctuations, and an increase in adverse events in iron users. Clinical practice should avoid disproportionately high ESA or iron doses to achieve hemoglobin targets, particularly in those with significant comorbidity or ESA resistance.