Tolerance induction is a fascinating option to prevent allergic diseases or allograft rejection. Calcitriol is the hormonal form of vitamin D and is produced by two hydroxylation steps: a hepatic 25-hydroxylation of vitamin D and a subsequent renal 1alpha-hydroxylation. Calcitriol has important immunomodulatory properties. Calcitriol can prevent those inflammatory processes which are responsible for allograft rejection, whereas its effects on immunological responses related to allergic reactions are more complex and not fully elucidated. This article summarizes present knowledge on vitamin D and the adaptive immune system. Experimental and clinical studies support the assumption that calcitriol can decrease the risk of allograft rejection. Prospective randomized clinical trials are however needed to clarify whether administration of calcitriol, some of its analogues, or simple vitamin D supplementation is able to prevent rejection in solid organ transplanted patients. With respect to allergic reactions, human data are inconsistent at present. Some argue that vitamin D deficiency may cause allergic reactions whereas others argue that vitamin D excess leads to an increased allergy risk. In this context, current strategy of vitamin D supplementation in infants and the possibility of a bimodal effect on allergic reactions of both, vitamin D deficiency and excess are discussed.