This brief review deals with the key trans- and cis-elements that are currently believed to participate in TH action at the transcriptional level. The reader is also referred to other recent reviews (53,54). In sum, there are multiple levels of complexity that make an understanding of the fundamental mechanisms of TH action difficult. However, the interactions of multiple TRs and TRAPS along with putative coactivators and ligands provide the cell with a wide range of biological responses. An appreciation of these phenomena will ensure insight into regulated gene expression in general, and the mode of action of TH in particular. While the field has progressed greatly since Jack Oppenheimer first described the nuclear binding of TH, there are "many more miles to go" for all of us, including Jack. We trust the journey will continue to be captivating.