Multidrug-resistant tuberculosis (MDR-TB), resistant to at least both isoniazid and rifampicin, poses a serious threat to global health because it requires treatment for a long duration and frequent hospitalization, and results in a considerable number of mortalities. According to a report from the World Health Organization in 2000, 3.2% of all new TB cases are MDR. In South Korea, multidrug-resistance was observed in 13% of re-treatment cases. The treatment of MDR-TB is difficult, since second-line drugs must be used, which are not as potent or as well tolerated as in the first-line drugs. Early publications on the treatment response of MDR-TB reported a considerable rate of mortality, as high as 37%. The use of 4 or 5 drugs including injectable drugs and fluoroquinolones is the fundamental of the medical treatment of MDR-TB. For patients with MDR-TB refractory to medical treatment, surgical resection could be tried. However, the candidate for the surgical resection should be selected cautiously. To overcome the low success rate of treatment among MDR-TB patients, well-designed clinical trials including newer drugs or regimens should be performed. MDR-TB has been a serious challenge to human health, especially in South Korea. To reduce the individual or social burden from MDR-TB, a commitment of government as well as clinicians is essential.