The scope of this review will be limited to highlighting the actions of 1 alpha ,25-dihydroxyvitamin D sub(3) (1,25(OH) sub(2)D sub(3)) mediated by nuclear vitamin D receptor (VDR) and discussing new developments in the structure/function analysis of the receptor, including the phenotype of VDR knockout mice and the biochemical classification of patients with point mutations in the receptor. These new advances, along with other recent research, will be interpreted to update our understanding of the molecular role of VDR, ranging from characterization of its natural gene and clinically significant polymorphisms, through its DNA contact sites and protein partners, to novel ligand analogs that hold the promise of influencing VDR conformation in a therapeutically beneficial fashion.