The emergence and spread of Mycobacterium tuberculosis strains resistant to multiple drugs represent a threat for global tuberculosis control. The World Health Organization (WHO) estimates that almost 500,000 cases of M. tuberculosis resistant to isoniazid and rifampicin (multidrug-resistant, or MDR-TB), at least, emerged in 2006. In addition, new cases of extensively drug-resistant tuberculosis (XDR-TB), defined as MDR-TB with resistance to a fluoroquinolone and at least one second line injectable agent, have been reported in 45 countries in all five continents. Multidrug-resistant tuberculosis is an emerging problem in Spain but the impact of this disease is limited: the WHO estimates that 0.1% of new cases of tuberculosis and 4.3% of previously treated cases are MDR-TB. Treatment of MDR-TB is especially complicated, since this disease requires the use of drugs that are less effective and more toxic, requiring treatment to be administered over longer periods and severely reducing the probability of success. This situation poses a serious problem for low income countries, especially those with a high prevalence of human immunodeficiency virus type 1 (HIV-1) infection. MDR-TB and XDR-TB are also of special concern in wealthy countries, due to mass immigration. Therefore, tuberculosis resistant to multiple drugs should be given high priority in global public health and biomedical research.