Antimicrobial resistance (AMR) is one of the world’s most pressing and urgent global health threats —one that could erode gains against tuberculosis (TB), malaria, HIV/AIDS, and many other infectious diseases. While AMR has emerged as a critical issue at the global level, current efforts to address AMR are insufficient to curb its spread. Immediate, cross-cutting, and multidisciplinary action is required to adequately address the multidimensional drivers of AMR. In the health sector, strengthening the systems through which health services and medicines are provided is a prerequisite to making progress against AMR. This technical brief discusses how SIAPS is working to address AMR through a health system strengthening approach with interventions spanning the global, regional, national, and local levels.