Tuberculosis (TB) remains a global health threat, and 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 prevalence and deaths and improving treatment outcomes for new smear-positive TB cases, the burden of TB remains enormous. SA has the means to overcome this situation. In addition to better implementing the basics of TB diagnosis and treatment, scaling up the use of Xpert MTB/RIF as a replacement for sputum smear microscopy, strengthening case finding in and beyond healthcare facilities and a greater focus on TB prevention for people living with HIV, particularly earlier initiation of and scaling up antiretroviral therapy and scaling up continuous isoniazid preventive therapy, will have a substantial impact on TB control. New TB drugs, diagnostics and vaccines are required to further accelerate progress towards improved TB control in SA and beyond.