Antibiotic-resistant bacterial infections have become a public health crisis. Their incidence has increased in the past decades, driven by the acquisition of antibiotic resistance genes (ARGs), but how these ARGs are acquired by bacteria in the environment is not completely known. Human interaction with the environment can spread resistant bacteria, further influencing the antibiotic resistance properties of environmental microbes. In a new study, researchers sought to characterize how human activities influence the environmental “resistome.” They surveyed the microbiome, resistome, and mobilome of planktonic microbial communities in the Han River. The study was extensive, with samples spanning the length of the river over three seasons. Using integrative metagenomic analyses, they found that fecal contamination from humans influenced the resistome in densely populated areas of the river, but interestingly, fecal bacteria weren’t the main factor influencing the ARG increase. Human-related mobile resistance genes were transferred to environmental relatives of clinically important bacteria, allowing the environmental bacteria to become resistant. Although future studies will determine the evolutionary mechanisms at play and how the environmental resistome influences clinical antibiotic resistance, this study provides novel insight into how human activities shape the environmental resistome.