This document presents the key findings from surveillance of antibiotic use and bacterial resistance to antibiotics for the year 2021 in human and animal health and the environment, focusing on common indicators, as well as actions implemented for prevention, infection control, and the appropriate use of antibiotics. It is intended for professionals in human, animal, and environmental health and is accessible to professionals who are not specialists in antibiotic resistance. The year 2021, still marked by the COVID-19 pandemic, reveals an overall maintenance of progress in terms of antibiotic consumption and antibiotic resistance compared to 2019, but also areas of concern regarding antibiotic prescriptions, particularly among the youngest in human health, as well as antibiotic resistance in both human and animal health. In the environmental sector, work continues to identify the most relevant indicators and standardize methods for collecting and analyzing the presence of antibiotics and resistance markers in the environment. Regarding the prevention of antibiotic resistance, the document describes the range of tools available to human health professionals for infection prevention and the proper use of antibiotics. It presents the social marketing campaign targeting the general public and healthcare professionals launched in 2022 by Santé publique France. In animal health, prevention efforts are driven by the Écoantibio plans, which combine regulatory changes with the development of tools and initiatives to support professionals’ commitment. The European Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections (EU-JAMRAI) and the establishment of the Promise meta-network led by Inserm support the development of "One Health" initiatives. European Antibiotic Awareness Day on November 18, 2022, and World Antimicrobial Stewardship Week aim to mobilize all stakeholders: citizens, patients, human and animal health professionals, environmental experts, and decision-makers. This document is the result of collaboration between Santé publique France and the ANSM, ANSES, the Health Insurance Fund, and the High Authority for Health, in conjunction with the Biodiversity, Health and Anthropogenic Activities of the General Commission for Sustainable Development, the Ministerial Mission for Infection Prevention and Antibiotic Resistance of the Ministry of Health and Prevention, the Office of Inputs and Public Health in Livestock of the Directorate General for Food, and their partners. It is carried out within the framework of the 2016 Interministerial Roadmap for Controlling Antibiotic Resistance, the 2022–2025 National Strategy for the Prevention of Infections and Antibiotic Resistance in Human Health, the Ecoantibio Plan for Animal Health, the Biodiversity Plan, and the National Health and Environment Plan.