Iron is a vital metal for the proliferation of all cells including those of the immune system. Iron deficiency causes several defects in both the humoral and cellular arms of immunity. One of the most profound changes is a reduction in peripheral T cells and atrophy of the thymus. The presence of transferrin receptor on immature, proliferating thymocytes and the inhibition of thymocyte proliferation and differentiation by anti-transferrin receptor antibody highlight the importance of iron to T cell development. Growing evidence suggests that T cells may in turn, regulate iron metabolism perhaps through interactions with the non-classical major histocompatibility complex gene HFE. The association of the iron transporter NRAMP1 with several autoimmune disorders along with evidence that iron can catalyze the production of cryptic epitopes of several autoantigens, establishes a potential role for iron in the development of autoimmunity.