The emergence and spread of antimicrobial resistance (AMR) and resistant bacteria, are a global public health challenge. Through horizontal gene transfer, potential pathogens can acquire antimicrobial resistance genes (ARGs) that can subsequently be spread between human, animal, and environmental reservoirs. To understand the dissemination of ARGs and linked microbial taxa, it is necessary to map the resistome within different microbial reservoirs. By integrating knowledge on ARGs in the different reservoirs, the One Health approach is crucial to our understanding of the complex mechanisms and epidemiology of AMR. Here, we highlight the latest insights into the emergence and spread of AMR from the One Health perspective, providing a baseline of understanding for future scientific investigations into this constantly growing global health threat.