The various physiological activities of 1,25-dihydroxyvitamin D3 (1,25D3) are mediated by the nuclear vitamin D receptor (VDR), making VDR a prime therapeutic target for associated pathologies, including not only bone disorders, but also autoimmune diseases and cancers. VDR shares with the nuclear receptor superfamily, structurally and functionally related DNA-binding and ligand-binding domains. It has been over 25 years since the first crystal structure of the human VDR ligand-binding domain was solved, highlighting the binding mode of 1,25D3 and its mechanism of action, and guiding drug discovery efforts. Since the original structure, a wealth of information on the recognition of natural ligands and synthetic analogs, and on mechanisms of action, has been obtained through structural analysis, primarily by X-ray crystallography of VDR complexes. During this period, progress has been made from our understanding of the structures of the isolated domains to almost complete 3D structures of VDR functional complexes bound to cognate DNA response elements by cryo-electron microscopy and structural mass spectrometry, advancing our understanding of the biology of VDR in response to ligand, DNA response element, and coregulator proteins and insights into allosteric regulation of receptor action. Here, we provide a compendium of VDR and focus on what has been learned from studies on VDR structures and dynamics about the mode of action, function, and therapeutic promise.