Organohalides are distributed widely in the environment and originate from both biological and industrial sources. Under aerobic conditions, these compounds are typically consumed by oxidative and hydrolytic metabolism. However, vertebrates also express the unusual ability to promote reductive dehalogenation of natural iodotyrosine derivatives related to the thyroid hormone thyroxine. Iodide recovery from these compounds is promoted by iodotyrosine deiodinase, an enzyme crucial for human health. This same enzyme has also been discovered in all metazoa sequenced to date as well as some bacteria. The role of reductive dehalogenation in these additional organisms is not yet clear. Investigations are currently designed to identify the origins of this enzyme, characterize its biological role in non-vertebrates and understand its catalytic mechanism that includes a role of its bound flavin. Flavin-dependent reactions are associated with a wide variety of metabolic transformations but its use in reductive dehalogenation is quite rare. Results of this research will help to expand the known repertoire of flavin chemistry and will guide its future use in bioremediation of organohalide pollutants.