The developing and adult brain is a main target organ of thyroid hormones (including the prohormone thyroxine and its active derivative tri-iodothyronine or T3). Mouse genetics offers a number of promising possibilities to study their pleiotropic infl uence on the central nervous system, and to distinguish it from their peripheral function. In the following, we review recent advances brought by mouse genetics in our understanding of thyroid hormone signaling in the brain, both during development and in the adult. We particularly emphasize on the latest fi ndings about thyroid hormone transporters and synthesis pathway which bring a new view on the regulation of thyroid hormone levels sensed by brain cells. Roles of the thyroid hormone receptors, which have been reviewed elsewhere are only briefly discussed.