Tuberculosis caused by Mycobacterium tuberculosis (Mtb) is a significant public health concern, exacerbated by the emergence of drug-resistant TB. The genetic triggers that aid in the evolution of MDR and XDR-TB are not fully understood. In an effort to identify novel genetic factors that evoke drug resistance in Mtb, we performed genome wide association analysis (GWAS). For the first time we identified a strong association between the mutations in the DNA repair genes and multidrug-resistant phenotype. I would present our recent efforts on the role of DNA repair genes in the context of evolution of drug resistance.