Although hereditary hemochromatosis (HHC) is relatively common, it is an uncommon indication for orthotopic liver transplantation (OLT). The diagnosis of HHC in patients with end-stage liver disease is difficult because many of these patients have elevated serum and tissue iron levels. Of patients undergoing OLT with iron stores in the range typical for HHC, approximately 10% are homozygous for the C282Y mutation. Most studies published to date noted decreased survival in patients who underwent OLT for HHC compared with those who underwent OLT for other indications. Death in patients with HHC was caused by increased infectious and cardiac complications. Decreased post-OLT survival in patients with iron overload appears to be independent of HFE gene status. This suggests that regardless of the cause, iron overload may be detrimental in patients undergoing OLT. Follow-up of patients undergoing OLT for HHC and case reports of the inadvertent transplantation of a liver from a donor with HHC has furthered our understanding of the pathophysiological state of iron overload in HHC.