It has been a little more than 20 years since the first appreciation that the biologically active hormonal form of the secosteroid vitamin D-classically categorized as a regulator of calcium/phosphorous metabolism and bone mineralization-can exert effects on cells of the immune system.

Since then a substantial literature has accumulated to suggest that these effects are exerted on multiple immune cell types, are predominantly suppressive at pharmacologic levels, and are potent enough to have true therapeutic potential in the management or prevention of immune-mediated diseases.

Less clear at present, however, are the physiological roles played by the vitamin D endocrine system in the regulation of normal and abnormal immune responses.

In this review, an appraisal of the current understanding of vitamin D-mediated immune regulation is presented that emphasizes progress towards its clinical application as well as the manner in which emerging models of normal immune function may facilitate a more complete understanding of its physiologic significance.