The skin is not only the organ for the photosynthesis of vitamin D3, but also a target tissue for its activated form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Vitamin D3 is absolutely essential for the development and maintenance of a healthy skeleton. Without an adequate source of vitamin D, children develop rickets and the elderly develop osteomalacia and exacerbation of osteoporosis. 1,25(OH)2D3 is a potent inhibitor of proliferation of epidermal cells and, with its analogs, it has been developed for the successful treatment of psoriasis. Not all psoriasis patients, however, respond to 1,25(OH)2D3 and its analogs. Evidence suggests that there may be a defect in the regulation of levels of mRNA for the vitamin D receptor in patients who have partial or no response to 1,25(OH)2D3 therapy. The degree of responsiveness to 1,25(OH)2D3 therapy may also be related to the allelic variations in the vitamin D receptor gene. Parathyroid hormone-related peptide is synthesized by the epidermis and is an endogenous antiproliferative factor. Parathyroid hormone-related peptide agonists and 1,25(OH)2D3 inhibit in vitro and in vivo epidermal proliferation, whereas parathyroid hormone-related peptide antagonists stimulate both epidermal proliferation and hair growth in vivo. Therefore, the calciotropic hormones 1,25(OH)2D3 and parathyroid hormone-related peptide have wide-ranging clinical applications in dermatology.