Multidrug-resistant tuberculosis (MDR-TB) with bacillary resistance to at least isoniazid and rifampicin in vitro is a worldwide phenomenon. Hot spots of the disease are found scattered in different continents. Prevention of its development through good tuberculosis control programmes operating under the directly observed therapy, short-course (DOTS) strategy is of paramount importance. However, with established MDR-TB, treatment with alternative and specific chemotherapy is necessary to achieve a beneficial outcome. Such an approach on a programme basis is currently known as the 'DOTS-Plus' strategy. Second-line (reserve) drugs utilized in the treatment of MDR-TB are generally less potent and more toxic, perhaps with the notable exceptions of some fluoroquinolones and injectable agents. Surgery has a distinct adjunctive role for the management of MDR-TB in selected patients. The emergence of extensively drug-resistant tuberculosis (XDR-TB), that is, MDR-TB with additional bacillary resistance to the fluoroquinolones and injectables, has provided a very alarming challenge to global health, as the disease currently has a low cure rate and high mortality. In order to combat XDR-TB, strengthening of DOTS and DOTS-Plus programmes is mandatory, especially in the face of surging HIV infection. Furthermore, more attention needs to be focused on developing new drugs with potent bactericidal and sterilizing activities and low side-effects, and above all, drugs that are affordable for communities worldwide.