These guidelines are based on the 3rd Edition of the WHO Guidelines (Published 2015) World Health Organization’s Guidelines for the treatment of malaria. Additional literature surveys have been undertaken. Factors that were considered in the choice of therapeutic options included effectiveness, safety, and impact on malaria transmission and on the emergence and spread of antimalarial drug resistance. On-going surveillance is critical given the spread of artemisinin resistance in Southeast Asia, although not yet confirmed anywhere in Africa. The guidelines on the treatment of malaria in South Africa aim to facilitate effective, appropriate and timeous treatment of malaria, thereby reducing the burden of this disease in our communities. This is essential to further reduce the malaria case fatality rates currently recorded in South Africa, to decrease malaria transmission and to limit resistance to antimalarial drugs.