Thyroid hormone (TH) plays important roles in metabolism, growth and differentiation. Thyroid hormone receptors (TRs) are ligand-regulatable transcription factors that bind both TH and DNA enhancer sequences in the promoter region of target genes where they can interact with co-repressor and co-activator complexes. These interactons, in turn, have consequent effects on transcription. This review describes studies on TH action from our laboratory examining the cellular localization and motility of TRs using green fluorescent fusion proteins, gene expression profiles of TH in WT and TRalpha and TRbeta KO mice, as well as general transcription factor and co-activator recruitment on the promoters of target genes by TH in chromatin immunoprecipitation assays.