It is well known that iron (Fe) is transported to the mitochondrion for heme synthesis. However, only recently has the importance of this organelle for many other facets of Fe metabolism become widely appreciated. Indeed, this was stimulated by the description of human disease states that implicate mitochondrial Fe metabolism. In particular, studies assessing various diseases leading to mitochondrial Fe loading have produced intriguing findings. For instance, the disease X-linked sideroblastic anemia with ataxia (XLSA/A) is due to a mutation in the ATP-binding cassette protein B7 (ABCB7) transporter that is thought to transfer [Fe-S] clusters from the mitochondrion to the cytoplasm. This and numerous other findings suggest the mitochondrion is a dynamo of Fe metabolism, being vital not only for heme synthesis but also for playing a critical role in the genesis of [Fe-S] clusters. Studies examining the disease Friedreich ataxia have suggested that a mutation in the gene encoding frataxin leads to mitochondrial Fe loading. Apart from these findings, the recently discovered mitochondrial ferritin that may store Fe in ring sideroblasts could also regulate the level of Fe needed for heme and [Fe-S] cluster synthesis. In this review, we suggest a model of mitochondrial Fe processing that may account for the pathology observed in these disease states.