The study of haemoglobin switching has represented a focus in haematology due in 
large part to the clinical relevance of the fetal to adult haemoglobin switch 
for developing targeted approaches to ameliorate the severity of the 
beta-haemoglobinopathies. Additionally, the process by which this switch occurs 
represents an important paradigm for developmental gene regulation. In this 
review, we provide an overview of both the embryonic primitive to definitive 
switch in haemoglobin expression, as well as the fetal to adult switch that is 
unique to humans and old world monkeys. We discuss the nature of these switches 
and models of their regulation. The factors that have been suggested to regulate 
this process are then discussed. With the increased understanding and discovery 
of molecular regulators of haemoglobin switching, such as BCL11A, new avenues of 
research may lead ultimately to novel therapeutic, mechanism-based approaches to 
fetal haemoglobin reactivation in patients.