Thyroid hormone action in the brain is the end result of a complex mechanism aimed towards the delivery of adequate amounts of the active hormone, triiodothyronine (T3), to the cellular sites of action1. T3, as thyroxine (T4), is produced in the thyroid gland, but in the central nervous system most T3 is formed from T4 by the action of type 2 deiodinase (D2). In the rat, it has been estimated that up to 80% of brain T3 is formed locally. T4 and T3 are metabolized to the inactive compounds rT3 and T2, respectively, by type 3 deiodinase (D3). Therefore, the intracellular concentration of T3 depends upon the relative activity of D2 and D3. T3 acts by binding to nuclear receptors and regulating gene expression. Another factor that is attracting interest is cellular transport of T4 and T3. In this article I review the role of each of these elements in the final action of thyroid hormone in the brain as well as their relevance in disease.