Antibiotic resistance is an ancient problem, owing to the co-evolution of 
antibiotic-producing and target organisms in the soil and other environments 
over millennia. The environmental "resistome" is the collection of all genes 
that directly or indirectly contribute to antibiotic resistance. Many of these 
resistance determinants originate in antibiotic-producing organisms (where they 
serve to mediate self-immunity), while others become resistance determinants 
only when mobilized and over-expressed in non-native hosts (like plasmid-encoded 
β-lactamases). The modern environmental resistome is under selective pressure 
from human activities such as agriculture, which may influence the composition 
of the local resistome and lead to gene transfer events. Beyond the environment, 
we are challenged in the clinic by the rise in both frequency and diversity of 
antibiotic resistant pathogens. We assume that clinical resistance originated in 
the environment, but few examples of direct gene exchange between the 
environmental resistome and the clinical resistome have been documented. Strong 
evidence exists to suggest that clinical aminoglycoside and vancomycin 
resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone 
resistance gene qnr have direct links to the environmental resistome. In this 
review, we highlight recent advances in our understanding of horizontal gene 
transfer of antibiotic resistance genes from the environment to the clinic. 
Improvements in sequencing technologies coupled with functional metagenomic 
studies have revealed previously underappreciated diversity in the environmental 
resistome, and also established novel genetic links to the clinic. Understanding 
mechanisms of gene exchange becomes vital in controlling the future 
dissemination of antibiotic resistance.