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Tuberculosis (TB) is an airborne infection. Though effective anti-TB drugs have been available for more than 50 years, over one-third of the world’s population is exposed to TB bacterium; deaths due to TB infection occur at high frequency every day worldwide. Today, drug-resistant TB, TB/HIV co-morbidity and poor health infrastructure are major challenges worldwide, particularly in less developed countries. The primary objective of the study was to assess the progress of TB control programs in twenty-two Eastern Mediterranean Region countries toward Millennium Development Goals (MDGs) including implementation of the Directly Observed Treatment, Short-course (DOTS). Also, the study was designed to explore TB/HIV co-morbidity and to assess some factors potentially associated with TB progress in the region. Secondary data, obtained from the World Health Organization, World Bank, and World Resource Institute on line databases were used. Paired samples t-test and bivariate correlation were conducted. Between 1990 and 2005, TB incidence had decreased 9%, TB prevalence had decreased 37% (statistically significant) and TB mortality had decreased 28%; nevertheless, MDG targets were not met. TB/HIV co-morbidity increased in the region especially in HIV-high burden countries. Though DOTS population coverage was increased to 94% in 2005, DOTS new smear-positive case detection rate was 61% (target 70%) and DOTS treatment success was 80% (target 85%). Thus, the 1991 Stop TB Partnership targets were not met. In spite of the progress of TB control programs in the EMR, MDGs and DOTs targets of 2005 were not obtained. Further efforts such as allocation of more resources, strengthening of TB surveillance systems, extension of drug-resistant TB and TB/HIV collaborative programs, and TB research are required to achieve MDGs by 2015 and to fully implement the new Stop TB Strategy in the region.