In 2014, WHO reported approximately 9.6 million new cases of tuberculosis (TB) in the world, more than half of which are contributed by developing countries in Asia and Africa. Lack of modern diagnostic tools, underreporting of the new cases and underutilization of directly observed therapy (DOT) remain a concern in developing countries. Transient resurgence of TB during the HIV epidemic has subsided and the annual decline has resumed in developed countries including the USA. In 2014 though, the rate of decline has slowed down resulting in leveling of TB incidence in the USA. In developed countries like the USA, the incidence of TB remains high in those with certain risk factors for TB. This group includes immunocompromised patients, particularly those with positive HIV infection. Others at high risk include those with diabetes, cancer, those taking immunosuppressive drugs, and those with other medical conditions that reduce host immunity. If we look at age and ethnicity, elderly patients are at higher risk of developing TB. African-American, foreign-born, and homeless populations are also at higher risk of developing tuberculosis. Virulence of the mycobacteria, and immunological and genetically mediated factors are also mentioned, but these topics are not the primary goal of this article. This review, thus discusses the epidemiology, host factors, and those at high risk for developing active TB. A brief review of the current trends in drug resistance of mycobacteria is also presented.