1,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃; 1,25-dihydroxycholecalciferol or calcitriol] is the active form of vitamin D₃, a lipid-soluble vitamin that plays a role in calcium and bone metabolism. Recently, vitamin D₃ has been shown to function in cancer prevention, immunity and cardiovascular regulation. 1,25(OH)₂D₃ exhibits physiological and pharmacological effects by activating the vitamin D receptor (VDR), a transcription factor of the nuclear receptor superfamily. 1,25(OH)₂D₃ plays a role in maintaining oral health through its effects on bone and mineral metabolism and innate immunity, and several VDR gene polymorphisms have been reported to be associated with periodontal disease. VDR ligands should prove to be useful in the treatment and prevention of periodontal disease. (J Oral Sci 51, 11-20, 2009)