Thalassemia is one of the most common genetic blood disorders and results from deficient synthesis of one or more of the globin subunits of hemoglobin—the protein molecule in red blood cells that is necessary for oxygen transport in the blood. Patients affected by the most severe form of the disease (thalassemia major or Cooley’s anemia) develop life-threatening anemia within the first 2 years of life and require lifelong blood transfusions for survival, in combination with chelation therapy to prevent or reduce progressive iron overload. To provide a forum for discussion of recent research and clinical advancements in understanding and treating thalassemia, the New York Academy of Sciences and the Cooley’s Anemia Foundation jointly presented the “Tenth Cooley’s Anemia Symposium” on October 18–22, 2015 in Rosemont, Illinois. This Annals issue presents a collection of papers stemming from this symposium. The papers, written by basic scientists, clinical investigators, and clinicians, cover a range of topics, including the biology of globin gene regulation and fetal hemoglobin induction; the evolving areas of stem cell transplant, gene therapy strategies, and gene editing; the biology of iron regulation and possible therapeutic interventions in the hepcidin regulatory system; and clinical issues in thalassemia treatment and imaging.