Vitamin D, acting through its active metabolite 1,25(OH)(2)D(3), exerts its influence on many physiologic processes in addition to the regulation of calcium and phosphate homeostasis. These processes include the immune system. Both the adaptive and innate immune systems are affected by 1,25(OH)(2)D(3) and its receptor, and the cells involved express not only the vitamin D receptor but also, in most cases, the enzyme CYP27B1, which produces 1,25(OH)(2)D(3). Both the vitamin D receptor and CYP27B1 can be constitutive or induced by the ligands that activate the immune processes in these cells, providing feedback loops that help regulate the immune response. In general, 1,25(OH)(2)D(3) suppresses most elements of the adaptive immune system while inducing most elements of the innate immune system. Thus 1,25(OH)(2)D(3) may be protective against various autoimmune diseases and may limit graft rejection by suppressing adaptive immunity while enhancing the first line of defense against invading microorganisms via upregulation of innate immunity.