Antimicrobial resistance (AMR) is a growing global health emergency that threatens the effectiveness of antibiotics essential for humans, animals, and environmental health within the One Health framework. It is fueled by inappropriate antimicrobial use in healthcare, agriculture, and veterinary medicine, alongside environmental contamination from pharmaceutical residues. Resistance is driven by genetic mutations, horizontal gene transfer, and ecological pressures that accelerate the spread of multidrug-resistant pathogens. In 2021, approximately 4.71 million deaths were associated with AMR and 1.14 million deaths were attributable to AMR. This chapter examines the health and economic consequences of AMR, including rising morbidity, mortality, prolonged hospitalization, and escalating treatment costs, particularly in vulnerable populations. It also highlights Asian responses: Japan’s stringent stewardship and regulation, Taiwan’s advanced surveillance, India’s public “Red Line” campaign, and Thailand’s national strategic plan on AMR. These experiences demonstrate that strong governance, innovation, and community engagement can mitigate resistance even in resource limited settings. The chapter concludes by underscoring the need for policy innovation, strengthened regional and global cooperation, and sustained public education to safeguard antibiotic effectiveness for future generations.