Multi-drug resistant TB is a threat to global TB control programs, including Vietnam. We have identified the predominant mutations responsible for drug resistance in M.tuberculosis isolates from Vietnam and developed rapid detection tests for izoniazid, rifampicin and fluoroquinolone resistant isolates. We have demonstrated that the Beijing genotype is not only associated with MDR TB, but with specific drug-resistance mutations which confer higher MIC to the drugs. Studies into the effect of drug resistant minimum inhibitory concentration (MIC) on outcome, novel mutational mechanisms, efflux pumps in fluoroqinolone resistance and the relationship between resistance mutations, strain genotype and pathogen fitness are on-going.