The intricate interplay of anemia and iron overload under the pathophysiological umbrella of ineffective erythropoiesis in non-transfusion-dependent β-thalassemia (NTDT) results in a complex variety of clinical phenotypes that are challenging to diagnose and manage. In this How I Treat article, we use a clinical framework rooted in pathophysiology to present four common scenarios of patients with NTDT. Starting from practical considerations in the diagnosis of NTDT, we delineate our strategy …