CYP11A1 is a key enzyme in steroid synthesis abundantly expressed in the adrenal, testis, ovary, and placenta. This article reviews recent studies on cis-regulatory elements and trans-regulators of the CYP11A1 promoter, with special focus on their tissue-specific regulation. Trans-regulators include tissue-specific factors such as SF-1, DAX-1, TReP-132, LBP, and GATA that regulate tissue-specific expression of CYP11A1. These tissue-specific factors interact with factors commonly present in most cells like AP-1, Sp1, and AP-2 to bring CYP11A1 transcription to full potential. These transcription factors stimulate CYP11A1 transcriptional activity through interaction with their specific cis-elements or through protein-protein interaction. The cis-element on the Cyp11a1 promoter was further characterized in vitro and in vivo. Mutation of the proximal SF-1-binding site results in down regulation of CYP11A1 in the adrenal and testis but not in the ovary and placenta, leading to attenuated corticosterone circadian rhythms and blunted stress response.