As a global health problem, antimicrobial resistance (AMR) crosses national borders, leading UN (United Nations) multilateral agencies to call for all countries to improve the stewardship of antibiotics in humans and animals. South American countries have changed their regulations regarding antibiotic use in livestock production. This literature review examines how far the five largest meat-producing countries in South America (Argentina, Brazil, Chile, Colombia, and Uruguay) have come in terms of the relevant legislation. Rules on market entry (marketing authorization and official distribution systems) are already set in all countries examined. Four countries do not allow growth promoters based on critically important antibiotics, and countries have also begun to set guidelines and minimum welfare and biosecurity requirements to reduce the therapeutic demand for antibiotics. Nonetheless, there are aspects related to the distribution, use, and disposal of antibiotics that need to be developed further. In conclusion, legislation in South American countries is moving towards the goals set by UN multilateral agencies, but more can be done. Differences between countries’ rules and the gold standards set by the World Organization for Animal Health (OIE), World Health Organization (WHO), and Food and Agriculture Organization of the United Nations (FAO) reveal possible adaptations to the countries’ realities. Further studies must examine compliance with the legislation already set and investigate other tools that can be used alongside legislation as a driving force to change stakeholder behaviour.