The vitamin D endocrine system plays a crucial role in regulation of calcium homeostasis and bone metabolism. Over the past two decades of research, there is a growing appreciation for the immunoregulatory role of vitamin D. Vitamin D deficiency is associated with numerous diseases characterized by inflammation, including malignancies, autoimmune disorders and chronic infections. Vitamin D suppresses parathyroid hormone secretion, adaptive immune response, cell proliferation, and at the same time promotes insulin secretion, innate immune response and stimulates cell differentiation. The review discusses present state of knowledge of a basic role of vitamin D in modulating different immunological properties, including lymphocyte activation and proliferation, differentiation of Th lymphocytes, production of specific antibodies and regulation of the immune response. Finally, clinical potential of vitamin D metabolites for modulating tissue-specific immune responses and for preventing and treating inflammatory disease and immune system disorders has been reported.