One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0.7% of the world's population, had 17% of the global burden of HIV infection, and one of the world's worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Government's response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART). Care for acutely ill AIDS patients and long-term provision of ART are two issues that dominate medical practice and the health-care system. Decisive action is needed to implement evidence-based priorities for the control of the HIV and tuberculosis epidemics. By use of the framework of the Strategic Plans for South Africa for tuberculosis and HIV/AIDS, we provide prioritised four-step approaches for tuberculosis control, HIV prevention, and HIV treatment. Strong leadership, political will, social mobilisation, adequate human and financial resources, and sustainable development of health-care services are needed for successful implementation of these approaches.