During the 1990s, multidrug-resistant (MDR) tuberculosis (TB), defined as resistance to at least isoniazid and rifampin, emerged as a threat to TB control, both in the United States and worldwide. MDR TB treatment requires the use of second-line drugs (SLDs) that are less effective, more toxic, and costlier than first-line isoniazid- and rifampin-based regimens. In 2000, the Stop TB Partnership's Green Light Committee was created to increase access to SLDs worldwide while ensuring their proper use to prevent increased drug resistance. While assisting MDR TB treatment programs worldwide, the committee encountered reports of multiple cases of TB with resistance to virtually all SLDs. To assess the frequency and distribution of extensively drug-resistant (XDR) TB cases, CDC and the World Health Organization (WHO) surveyed an international network of TB laboratories. This report summarizes the results of that survey, which determined that, during 2000-2004, of 17,690 TB isolates, 20% were MDR and 2% were XDR. In addition, population-based data on drug susceptibility of TB isolates were obtained from the United States (for 1993-2004), Latvia (for 2000-2002), and South Korea (for 2004), where 4%, 19%, and 15% of MDR TB cases, respectively, were XDR. XDR TB has emerged worldwide as a threat to public health and TB control, raising concerns of a future epidemic of virtually untreatable TB. New anti-TB drug regimens, better diagnostic tests, and international standards for SLD-susceptibility testing are needed for effective detection and treatment of drug-resistant TB.