Multidrug-resistant bacteria are a threat to both human and animal health worldwide. Bacteria often gain resistance to drugs by collecting antibiotic resistance genes (ARGs) from other bacteria. One potential hotbed for this exchange is wastewater treatment plants (WWTPs), where environmental bacteria co-mingle with human/animal-associated bacteria. Unfortunately, little is known about the epidemiology of multidrug-resistant bacteria in WWTPs. To close this gap, researchers isolated 82 multidrug-resistant bacterial strains from WWTPs and compared their genomes to bacterial genomes found in public databases. Most multidrug-resistant bacteria were not closely related to human/animal-associated bacteria, and those that were closely related had distinct plasmid profiles compared to relatives. Plasmids, as opposed to chromosomes, were also the main carriers of ARGs. Some ARG-bearing plasmids had signs of transfer between WWTP-isolated and human/animal-associated bacteria, and the potentially transferred ARGs were associated with flanking insertion sequences, which are sequences that facilitate the movement of genes within a genome. This suggests that there is synergy between plasmids and insertion sequences during these gene transfers. While this study only examined a narrow set of multidrug-resistant isolates, these results highlight the important role plasmids play in the transmission of multidrug resistance in WWTPs.