Withholding iron from potential pathogens is a host defense strategy. There is evidence that iron overload per se compromises the ability of phagocytes to kill microorganisms. Several hypotheses exist to explain the association of hemochromatosis with infection. A combination of mechanisms likely contributes to the increase in susceptibility to infection in these patients. A review of the current literature delineating various pathogens to which patients with hemochromatosis are potentially susceptible, and recent advances in the understanding of the association of hemochromatosis with infection, are discussed.