Thyroid hormones and their metabolites are active regulators of gene expression, mitochondrial function and various other physiological actions in different organs and tissues. These actions are mediated by a spatio-temporal regulation of thyroid hormones and metabolites within a target cell. This spatio-temporal resolution as well as classical and non-classical actions of thyroid hormones and metabolites is accomplished and regulated on multiple levels as uptake, local activation and signaling of thyroid hormones. In this review, we will give an overview of the systems involved in regulating the presence and activity of thyroid hormones and their metabolites within the brain, specifically in neurons. While a wealth of data on thyroxin (T4) and 3,5,3’-triiodothyronine (T3) in the brain has been generated, research into the presence of action of other thyroid hormone metabolites is still sparse and requires further investigations. Display omitted •TH and their metabolites are present within the brain.•TH and their metabolites control various actions in the brain, specifically in neurons.•Transporters, deiodinases, and (non-) nuclear receptors mediate spatio-temporal regulations.