Guidelines on Implementation of Antimicrobial Stewardship in South Africa: One Health Approach & Governance (hereafter termed AMS One Health & Governance Guide) is intended to act as a blueprint for the steps to be taken by South African healthcare and veterinary workforce to enact AMS at national, provincial, district and health establishment levels as appropriate, in line with the Strategic Framework and Implementation Plan. It aims to provide a practical, step-by-step or ‘how to’ guide, addressing the governance framework at each level of the health system. National guidelines for management of multi-drug-resistant tuberculosis and HIV are already the subjects of national programs and updated regularly. Although this guide pertains to the stewardship of all antimicrobials, its focus will be on stewardship of antibiotics used to treat bacterial infections other than tuberculosis, addressing the gaps relating to antibiotic stewardship from an overarching, national perspective. As the approach to stewardship of antifungals shares the same principles as that of antibiotics, the suggested interventions can be applied equally to antifungals.