The emergence of multidrug-resistant (MDR) and, more recently, of extensively drug resistant (XDR) strains of Mycobacterium tuberculosis is a real threat to achieve tuberculosis (TB) control and elimination globally. More than 510,000 new cases of MDR-TB occur each year and XDR-TB cases are recognized in every setting where there has been the capacity to detect them, particularly in Eastern Europe. MDR- and XDR-TB control in Europe and the United States are heavily affected by what happens globally, as the majority of cases occurring in these countries originate in high TB-burden areas of the world. Scaling-up of culture- and drug susceptibility testing capacities and the expanded use of high-technology assays for rapid determination of resistance represent the prerequisites to achieve better control of MDR- and XDR-TB. Most cases with MDR- and XDR-TB in Europe and the United States can be treated successfully if well-designed regimens based on available second- and third-line anti-TB drugs are used and surgical options are carefully considered. Nevertheless, the development of new (more effective and less toxic) drugs to treat patients infected by MDR- and XDR-TB strains with or without active disease are urgently needed. Adherence to internationally agreed standards of care and control practices is imperative to achieve TB control.