Tuberculosis (TB) is one of the major emerging universal public health prob- lems. In 1993, WHO has declared TB as a global emergency, but its control is hampered due to multidrug resistance (MDR), i.e., Mycobacterium tuberculosis (M. tuberculosis) strains that are resistant to isoniazid (INH) and rifampicin (RIF), the two widely used drugs for treating TB. Recently, extensively drug-resistant (XDR) TB has been reported, as these are resistant not only to INH and RIF, but also to any fluoroquinolone drug in ad- dition to one of the three injectable second-line drugs (amikacin, kanamycin, and capreo- mycin). Following the invention of drugs having antitubercular (anti-TB) activity, multi- drug therapy has been responsible to control TB. Developments in molecular biology due to sequencing of the genome of M. tuberculosis have improved the understanding of anti- TB drug resistance. However, better information of drug resistance and molecular biology aspects have im- proved the current techniques of rapid detection of TB that will help to stimulate exploration of new targets for drug action. This review summarizes the molecular biology of drug resistance to the main classical drugs as well as drugs that are currently under developmental stage.