Bacteria have evolved resistance to all classes of antibiotics in current clinical use. The mechanisms of resistance include modification of antibiotic targets, altered uptake and active efflux, and the expression of enzymes that inactivate antibiotics. Many of the genes that encode antibiotic resistance in the clinic are circulated on mobile genetic elements such as plasmids and transposons resulting in rapid horizontal transfer of antibiotic resistance through bacterial populations as a consequence of antibiotic exposure and subsequent selection. Surveys of environmental bacteria reveal that these organisms harbor a remarkable collection of antibiotic resistance elements. Resistance is not limited to natural products, but also to their semi-synthetic derivatives and to completely synthetic antibiotics as well. Furthermore, the associated resistance genes encode proteins that are highly similar to the resistance elements in the clinic. Environmental bacteria therefore may be reservoirs of antibiotic resistance genes with the potential to be mobilized into pathogenic bacteria. Study of resistance in the environment therefore can inform on resistance that has or will emerge in the clinic.