The advent of antibiotics for the treatment of tuberculosis (TB) represented a 
major breakthrough in the fight against the disease. However, since its first 
use, antibiotic therapy has been associated with the emergence of resistance to 
drugs. The incorrect use of anti-TB drugs, either due to prescription errors, 
low patient compliance, or poor quality of drugs, led to the widespread 
emergence of Mycobacterium tuberculosis strains with an expanding spectrum of 
resistance. The spread of multidrug-resistant (MDR) strains (ie, strains 
resistant to both isoniazid and rifampicin) has represented a major threat to TB 
control since the 1990s. In 2006, the first cases of MDR strains with further 
resistance to fluoroquinolone and injectable drugs were described and named 
extensively drug-resistant TB (XDR-TB). The emergence of XDR-TB strains is a 
result of mismanagement of MDR cases, and treatment relies on drugs that are 
less potent and more toxic than those used to treat drug-susceptible or MDR 
strains. Furthermore, treatment success is lower and mortality higher than 
achieved in MDR-TB cases, and the number of drugs necessary in the intensive 
phase of treatment may be higher than the four drugs recommended for MDR-TB. 
Linezolid may represent a valuable drug to treat cases of XDR-TB. Delamanid, 
bedaquiline, and PA-824 are new anti-TB agents in the development pipeline that 
have the potential to enhance the cure rate of XDR-TB. The best measures to 
prevent new cases of XDR-TB are the correct management of MDR-TB patients, early 
detection, and proper treatment of existing patients with XDR-TB.