Tuberculosis remains a global epidemic, with one-third of the population infected and 9 million active cases. Mono- and multidrug resistance in 6 World Health Organization (WHO) regions have been assessed in 40% of the global cases diagnosed by positive results of sputum testing. The 2004 report of the WHO Global Project on Anti-Tuberculosis Drug Resistance Surveillance confirms earlier findings that drug-resistant tuberculosis is ubiquitous and that multidrug-resistant tuberculosis has increased alarmingly. Control of tuberculosis, which is undermined by the human immunodeficiency virus (HIV) epidemic, is seriously jeopardized by multidrug resistant strains, for which treatment is complex, more costly, and less successful. Challenges for high-burden countries include implementation of the DOTS strategy and management of identified multidrug resistance with DOTS-Plus. Strengthening of the laboratory network in conjunction with improvement of surveillance, elucidation of the impact of HIV on transmission of tuberculosis and on amplification of resistance at individual and population levels, and implementation of private sector policies on drug resistance are imperative. New diagnostic tools and drugs are needed to expedite early detection and cure of multiresistant strains.