Vitamin D plays a major role in bone mineral density and calcium homeostasis. Apart from its classical action, the active form of vitamin D [1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))] influences the innate and adaptive immune functions through vitamin D receptor (VDR) that are present in various cells of the immune system. Vitamin D deficiencies have been associated with development of tuberculosis (TB) disease, caused by Mycobacterium tuberculosis. Vitamin D(3) is shown to enhance macrophage phagocytosis of M. tuberculosis and increases the production of antimicrobial peptide cathelicidin and killing of M. tuberculosis. During the preantibiotic era, exposure to sunlight and supplementation of vitamin D were the methods of choice for treatment of TB. Vitamin D supplementation showed sputum clearance and radiological improvement and reduction in mortality among human immunodeficiency virus (HIV)-infected patients with TB. VDR gene polymorphisms regulate the immunomodulatory effect of vitamin D(3) and are associated with faster sputum conversion during anti-TB treatment. The emerging evidences regarding immunomodulatory properties of vitamin D(3) have rekindled interest in vitamin D as an adjunct to anti-TB therapy. The current review explains the important potential application of vitamin D in enhancing the innate immunity to TB and the role of VDR gene variants on anti-TB treatment.