Thyroid hormones and thyroid hormone receptors (TRs) confer a fundamental regulation of critical genes involved in metabolism, differentiation, and development. A similar role is attributed to the highly conserved zinc-finger factor CTCF. Furthermore, a potential role in tumour suppression has been attributed to CTCF. In addition to promoter regulation, CTCF has also been shown to be involved in chromatin insulation or enhancer blocking. In several cases, binding sites for TR and for CTCF have been found next to each other. Functionally, these sites mediate synergistic repression or induction dependent on the type of binding site and on the presence or absence of thyroid hormone. Here we discuss functional similarities between TR and CTCF and their roles within these composite elements.