Thyroid hormones exert pleiotropic effects at the cell level and several theories to define the initial site of action have been proposed. First mitochondria, nuclei or plasma membrane were considered as the main regulatory step. More recently, evidence of T3 and/or T4 binding sites present in different cellular compartments suggests the existence of more than one initial site of action. Binding sites from cytosol or plasma membrane and endoplasmic reticulum seem to participate either in the storage of thyroid hormones, or in their intracellular transport and metabolism. Mitochondrial and certain plasma membrane binding sites could be responsible for rapid effects of thyroid hormones at their level. Nuclear T3 binding sites located in the chromatin are considered as a true hormone receptor and are more documented in a structural and functional point of view. They may mediate thyroid hormone effects on the regulation of DNA transcription and the synthesis of active proteins. Their mechanism of action is nevertheless not well defined.