The regulation of mineral homeostasis involves the three mineralotropic hormones PTH, FGF23 and 1,25-dihydroxyvitamin D3(1,25(OH)2D3). Early research efforts focused on PTH and 1,25(OH)2D3and more recently on FGF23 have revealed that each of these hormones regulates the expression of the other two. Despite early suggestions of transcriptional processes, it has been only recently that research effort have begun to delineate the genomic mechanisms underpinning this regulation for 1,25(OH)2D3and FGF23; the regulation of PTH by 1,25(OH)2D3, however, remains obscure. We review here our molecular understanding of how PTH inducesCyp27b1expression, the gene encoding the enzyme responsible for the synthesis of 1,25(OH)2D3. FGF23 and 1,25(OH)2D3, on the other hand, function by suppressing production of 1,25(OH)2D3. PTH stimulates the PKA-induced recruitment of CREB and its coactivator CBP at CREB occupied sites within the kidney-specific regulatory regions ofCyp27b1. PKA activation also promotes the nuclear translocation of SIK bound coactivators such as CRTC2, where it similarly interacts with CREB occupiedCyp27b1sites. The negative actions of both FGF23 and 1,25(OH)2D3appear to suppressCyp27b1expression by opposing the recruitment of CREB coactivators at this gene. Reciprocal gene actions are seen atCyp24a1, the gene encoding the enzyme that degrades 1,25(OH)2D3, thereby contributing to the overall regulation of blood levels of 1,25(OH)2D3. Relative to PTH regulation, we summarize what is known of how 1,25(OH)2D3regulates PTH suppression. These studies suggest that it is not 1,25(OH)2D3that controls PTH levels in healthy subjects, but rather calcium itself. Finally, we describe current progress using anin vivoapproach that furthers our understanding of the regulation ofFgf23expression by PTH and 1,25(OH)2D3and provide the first evidence that P may act to induceFgf23expression via a complex transcriptional mechanism in bone. It is clear, however, that additional advances will need to be made to further our understanding of the inter-regulation of each of these hormonal genes.