Hereditary hemochromatosis (HH) is one of the most common genetically 
transmitted conditions in individuals of Northern European ancestry. The disease 
is characterized by excessive intestinal absorption of dietary iron, resulting 
in pathologically high iron storage in tissues and organs. If left untreated, HH 
can damage joints and organs, and eventually lead to death. There are four main 
classes of HH, as well as five individual molecular subtypes, caused by 
mutations in five genes, and the approaches implemented in the discovery of each 
HH type have specific histories and unique aspects. In this chapter, we review 
the genetics of the different HH types, including the strategies used to detect 
the causal variants in each case and the manner in which genetic variants were 
found to affect iron metabolism.