Zizanoic acid is a sesquiterpene in vetiver oil. Zizanoic acid exhibited significant antimycobacterial activity against drug-resistant mutants of M. smegmatis and virulent strain H37Rv of M. tuberculosis. These observations may be of great help in the QSAR-based antimycobacterial drug designing from a very common, inexpensive and non-toxic natural product for the management of MDR and XDR tuberculosis.