Treatment failure linked to antimicrobial resistance (AMR) is one of the most important threats to human health. The genes that encode AMR have become highly mobile, with extrachromosomal elements called plasmids acting as their primary vectors worldwide. It is becoming increasingly common for a single bacterial cell to carry one or more plasmids conferring resistance to multiple frontline, or even last-line treatments. Despite the pivotal role of plasmids in the emergence of multidrug-resistant (MDR) pathogens and community and hospital outbreaks, little is known about where resistance plasmids come from and how plasmids evolved to become the global spreaders of AMR we face today. In this talk, I will present the findings from our latest study on the evolution of plasmids throughout the antibiotic epoch. By reconstructing historical plasmids from bacterial pathogens isolated in the pre-antibiotic era, we reveal their modern descendants, the evolutionary trajectories they have followed over the past 100 years and their molecular fate. In doing so, we show how the anthropogenic introduction of antibiotics influenced plasmid evolution and the emergence of MDR vectors currently spreading AMR around the globe. Finally, we used our data to propose a new model of plasmid evolution, which involves the continuous death and birth of plasmids via a cycle of fragmentation, recycling and genome fusion driving the constant emergence of new gene vectors.