South Africa (SA) has one of the world’s worst TB epidemics driven by HIV. Among the 22 countries with the highest burden of TB, SA has the highest estimated incidence and prevalence of TB, the second highest number of diagnosed multidrug-resistant TB cases, and the largest number of HIV-associated TB cases. Although SA has made notable progress in reducing TB notification rates and improving treatment outcomes, the burden of TB remains enormous. South Africa has the largest absolute number of HIV-infected individuals in the world. Despite a massive, publically funded antiretroviral therapy program, high HIV incidence and ongoing HIV-related mortality remain.