G protein-coupled receptors (GPCRs) participate in a variety of physiological functions and are major targets of pharmaceutical drugs. More than 600 GPCRs have been identified in the human genome. Although GPCRs are expressed in multiple tissues and individual tissues express multiple GPCRs, many have exclusive or increased expression within the central nervous system (CNS). These unique and diverse expression patterns raise fundamental questions as to the molecular mechanisms underlying the tissue/cell-specific distribution of GPCRs as well as the means by which their expression is altered in response to stimuli. Gene expression in mammals involves both transcriptional and posttranscriptional mechanisms. In this chapter, we provide an overview of the transcriptional regulation of GPCRs and discuss both established and emerging techniques to study transcriptional regulation.