Nucleotide excision repair (NER) is one of the most extensively studied DNA repair processes in both prokaryotes and eukaryotes. The NER pathway is a highly conserved, ATP-dependent multi-step process involving several proteins/enzymes that function in a concerted manner to recognize and excise a wide spectrum of helix-distorting DNA lesions and bulky adducts by nuclease cleavage on either side of the damaged bases. As such, the NER pathway of Mycobacterium tuberculosis (Mtb) is essential for its survival within the hostile environment of macrophages and disease progression. This review focuses on present published knowledge about the crucial roles of Mtb NER proteins in the survival and multiplication of the pathogen within the macrophages and as potential targets for drug discovery.