In July 2020, a targeted testing strategy was developed to address South Africa’s testing response to COVID-19. This strategy was developed to accommodate the country’s constrained testing capacity, to deal with the testing backlog, and to ensure that those categories of patients with an urgent clinical need were prioritised for testing. Symptomatic hospitalised patients, as well as healthcare workers, were therefore prioritised for testing. This guidance was updated in October 2020 for South Africa to utilise its expanded COVID-19 testing resources to support all components of the COVID-19 response. This guide seeks to address practical considerations regarding the implementation of SARS-CoV-2 Ag-RDTs. It provides support for healthcare providers, health facility managers, casualty staff and community outreach testing teams regarding the implementation of antigen testing. The document covers all aspects of the use of the antigen test and reporting of results, and is applicable in both the public and private sectors.