The global spread of multidrug-resistant strains of tuberculosis (TB) mycobacteria was one of the main reasons leading the World Health Organisation to launch the Stop TB program worldwide. In spite of a slow decline of TB incidence and mortality worldwide, multidrug-resistant TB (MDR-TB) has increased in several countries. MDR-TB is caused by organisms that are resistant to at least isoniazid and rifampicin. The most drug-resistant forms of TB are the extensively drug-resistant TB (XDR-TB) strains caused by organisms that are resistant also to fluoroquinolones and any of the second-line anti-TB injectable drugs. XDR-TB can take 2 years or more to treat with drugs that are less effective, more toxic, and more expensive. Mortality for XDR-TB is very high, and the risk of the transmission between persons of XDR-TB strains is a matter of concern for health systems. Major issues associated with enhanced XDR-TB are non-implementation of DOT (directly observed therapy) and DOT expansion strategies, the insufficient supply or the poor quality of the anti-tuberculosis drugs, and the inadequate intake of the anti-tuberculosis medicines. Nevertheless, prior treatment of MDR-TB with second-line drugs is the strongest associated factor increasing the risk for XDR tuberculosis more than fourfold. Specialized rapid, effective diagnostic methods, including drug-sensitivity testing, are essential for a precise diagnosis of XDR-TB, and subsequent proper treatment. The global rise and spread of XDR-TB have serious effects on TB-control programs, and urge effective health policy responses. National TB control programmes working with all health services can prevent XDR-TB by ensuring that all the physicians and professionals caring for people with TB adhere to the International Standards for TB Care. Specialized centres at regional and national levels should be dedicated to care for difficult-to-treat and untreatable patients with XDR-TB.
