Haematopoiesis during mammalian development is characterised by the progressive appearance of distinct populations of cells at stage-specific sites within the developing embryo. The earliest “primitive” haematopoietic cells appear in the yolk sac, before being later replaced by “definitive” cells, located first in the aorta-gonad mesenephros, then the foetal liver and finally in bone marrow of the adult. In concert with the progression from primitive to definitive haematopoiesis, the developing erythroid system expresses developmentally-specific forms of haemoglobin, in a process known as haemoglobin switching. The pattern of globin gene expression during development is the result of a complex series of regulatory events. Numerous epigenetic and transcriptional regulators are required for switching to occur, but the process remains incompletely understood.  The study of hemoglobin switching has been stimulated by recognition of the therapeutic potential of globin switching in the setting of the inherited β-haemoglobinopathies. Hereditary persistence of foetal haemoglobin (HPFH) is a non-pathological condition in which the silencing of the foetal γ-globin gene is reduced or absent, resulting in the persistent expression γ-globin after birth. Co-inheritance of HPFH with β-thalassaemia or sickle cell disease genotypes results in milder symptoms, due to complementation of the mutant β-globin by the γ-globin. A greater understanding of the process whereby γ-globin is silenced is therefore of clinical significance, with the ultimate goal of identifying therapeutic strategies capable of reactivating γ-globin expression in the adult. This aim has been the driving force behind the generation of several model systems by my laboratory that recapitulate the foetal to adult haemoglobin expression pattern throughout development and disease.