Context 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. Objective 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. Data Sources 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. Study Selection 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. Data Extraction 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. Data Synthesis 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 (Conclusion 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.