Hemoglobin is a tetramer comprising 2 α-like and 2 β-like globin chains encoded by genes in the unlinked α- and β-globin loci. Globin gene expression is regulated by distal enhancers (yellow boxes). The γ-globin gene is expressed during fetal life where it contributes to HbF but is silenced around the time of birth. However, normal adults express a small but variable amount of γ-globin in a small proportion of red cells called F cells. The question addressed here is what underlies γ-globin expression in the small numbers of HbF-containing cells. Answering this underlies strategies for therapeutic reexpression of γ-globin in adult life, which has the potential to ameliorate, or even cure, the major hemoglobinopathies, β-thalassemia and sickle cell disease.