The United Nations Millennium Development Goals (MDGs) are stimulating more rigorous evaluations of the impact of DOTS (the WHO-recommended approach to tuberculosis control based on 5 essential elements) and other possible strategies for tuberculosis (TB) control. To evaluate the prospects for detecting 70% of new sputum smear-positive cases and successfully treating 85% of these by the end of 2005, for reducing TB incidence, and for halving TB prevalence and deaths globally between 1990 and 2015, as specified by the MDGs. TB case notifications (1980-2003) from DOTS and non-DOTS programs and cohort treatment outcomes (1994-2002) reported annually to the World Health Organization (WHO) by up to 200 countries, TB death registrations, and prevalence surveys of infection and disease. Case notification series that reflect trends in incidence, treatment outcomes from DOTS cohorts, death statistics from countries with WHO-validated vital registration systems, and national prevalence surveys of infection and disease. Case reports, treatment outcomes, prevalence surveys, and death registrations from WHO's global TB database covering 1990-2003 to estimate TB incidence, prevalence, and death rates through 2015 for 9 epidemiologically different world regions. TB incidence increased globally in 2003, but incidence, prevalence, and death rates were approximately stable or decreased in 7 of 9 regions. The exceptions were regions of Africa with low (<4% in adults 15-49 years) and high rates (> or =4%) of HIV infection. The global detection rate of new smear-positive cases by DOTS programs increased from 11% in 1995 to 45% in 2003 (with the lowest case-detection rates in Eastern Europe and the highest rates in the Western Pacific) and could reach 60% by 2005. More than 17 million patients were treated in DOTS programs between 1994 and 2003, with overall treatment success rates more than 80% since 1998. In 2003, overall reported treatment success was 82%, with much variation among regions. The highest rates were reported in the Western Pacific region (89%) and lowest rates in African countries with high and low HIV infection rates (71% and 74%, respectively), in established market economies (77%), and in Eastern Europe (75%). To halve the prevalence rate by 2015, TB control programs must reach global targets for detection (70%) and treatment success (85%) and also reduce the incidence rate by at least 2% annually. To halve the death rate, incidence must decrease more steeply, by at least 5% to 6% annually. Reduction of TB incidence, prevalence, and deaths by 2015 could be achieved in most of the world, but the challenge will be greatest in Africa and Eastern Europe.