Tuberculosis (TB) causes maximum mortality and morbidity worldwide. 25 per cent of the global population harbour Mycobacterium tuberculosis (Mtb) and therefore are at risk of developing active disease. Of late, the disseminated diseases of TB are on the increase. Nearly one-third of all TB infections can be classified as extrapulmonary-TB (EPTB). TB can spread to the bone, brain, intestine, peritoneum, genitourinary system, and female genital sites leading to problems of conception. Therefore undoubtedly, TB has turned out to be a tremendous public health problem globally. The emergence of drug-resistant bacteria calls for new anti-tuberculous drugs to enhance response to antimicrobial therapy for active TB. However, discoveries of very effective anti-TB new medicines have not materialised yet. Thus, nutritional anti-TB intervention is highly important. In the pre-antibiotic era, Vitamin D was used for the treatment of TB. Its active component 1,25-dihydroxy-vitamin D3 was shown to display anti-TB activity in vitro. Vitamin D deficient humans display greater susceptibility to TB. Vitamin D deficiency induces worse disease progression in TB cases as observed in many clinical trials. The efficacy of the addition of vitamin D supplements in TB treatment has also been estimated. Thus, by now, the role of vitamin D in TB prevention and treatment is well established. Knowledge of the molecular mechanism of vitamin D is crucially vital for new anti-TB drug design. This review article discusses the recent advancement regarding the molecular mechanism of vitamin D-related anti-TB action. Further elucidation of this area may help novel anti-TB drug development.