Thyroid hormone (TH) is essential for normal brain development, but the specific actions of TH differ across developmental time and brain region. These actions of TH are mediated largely by a combination of thyroid hormone receptor (TR) isoforms that exhibit specific temporal and spatial patterns of expression during animal and human brain development. In addition, TR action is influenced by different co-factors, proteins that directly link the TR protein to functional changes in gene expression. Several recent studies now show that TRs may be unintended targets of chemicals manufactured for industrial purposes, and to which humans and wildlife are routinely exposed. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and bisphenol-A (BPA), and specific halogenated derivatives and metabolites of these compounds, have been shown to bind to TRs and perhaps have selective effects on TR functions. A number of common chemicals including polybrominated biphenyls (PBBs) and phthalates may also exert such effects. Considering the importance of TH in brain development, it will be important to pursue the possibilities that these chemicals - or interactions among chemical classes - are affecting children's health by influencing TH signaling in the developing brain.