Thyroid hormones are essential to normal brain development. Many studies using brain cell cultures have provided evidence of the direct action of thyroid hormones on nerve cells The cellular actions of thyroid hormones are mediated on target gene expression by several types of receptors, which are classified into α and β subtypes. These receptors have distinct spatial and temporal distributions, strongly suggesting that they have distinct functions during brain development. The respective role of each receptor, however, remains largely unknown. Only a few neuronal genes have been shown to be directly regulated by thyroid hormones. The complexity of regulation of gene expression by thyroid hormones is emphasized by the fact that their receptors may interact with other members of the nuclear receptor superfamily. In addition, the mechanisms of phosphorylation, which seems to play a key role in controlling these regulatory proteins, increase the complexity of the molecular action of thyroid hormones at the gene level during brain development.