Control measures have substantially reduced the historical distribution of malaria in South Africa; the country's population currently at risk for contracting malaria is approximately 4.3 million, predominantly in the northern and eastern border areas. The major strategies for malaria control are vector control through indoor residual spraying, case management, disease surveillance, epidemic preparedness and response, and public awareness. There has been a significant and sustained decrease in malaria case notifications since 2000, as a result of intensive indoor residual spraying including the use of DDT to combat insecticide-resistant Anopheles funestus; the introduction of artemisinin combination therapy; and the Lebombo Spatial Initiative, a cross-border collaboration targeting malaria in eastern Swaziland, southern Mozambique and northern KwaZulu-Natal (KZN). Rapid malaria antigen detection tests are widely used for diagnosis at primary health care level. HIV-malaria co-infected patients who are malaria non-immune are at risk for severe malaria. Renal failure has been identified as a particular complication in this group of patients. Despite successes in malaria control in South Africa, many challenges remain.