As antimicrobial use continues to rise, we are experiencing a concomitant rise in the prevalence of antimicrobial resistance. The precise relationship between use and resistance, however, has been challenging to define. Although the selection pressure exerted by antibiotic therapy appears to be the primary force promoting resistance, it is clear that the pathway to resistance is different for various organisms and antimicrobial agents. By understanding the mechanisms by which resistance emerges and spreads, it should be possible to design intervention strategies to slow or halt the process. This review summarizes some of our current understandings about the development and transmission of antibiotic-resistant bacteria, some of the control measures designed to interrupt the process, and how mathematical modeling can help us to better understand these complex pathways.