Steroid hormones are essential for normal sexual development, accommodation to stress, and regulation of fluid and electrolyte balance. Biosynthesis of these different classes of steroids and its appropriate regulation requires the precisely controlled expression of six different cytochrome P-450 enzymes and two hydroxysteroid dehydrogenases in different tissues. The molecular mechanism of the tissue-specific and pituitary hormone-regulated expression of the genes encoding P-450 enzymes in the steroidogenic tissues is the central problem of long-term regulation of steroidogenesis. Orphan members of the nuclear receptor superfamily play an important role in mediating transcriptional regulation of several steroid hydroxylase genes. Two of these transcription factors, steroidogenic factor-1 (SF-1) and DAX-1, will be reviewed here in detail.