The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) has changed dramatically over the past 15 years. Initially a nosocomial pathogen, newly emergent strains of MRSA have become increasingly common in the community among individuals lacking contact with healthcare. More recently, a third group of MRSA strains have been identified in association with livestock, particularly swine. These strains, termed livestock-associated MRSA, have now been identified in Europe, North America, and Asia in humans and animals. One molecular type, ST398, has been the dominant strain of livestock-associated MRSA identified to date. The emergence of this strain in animals and humans will be described in this review, including colonization and clinical infections caused by this strain. We also discuss lingering research questions and implications for controlling spread of this bacterium in an agricultural environment and beyond.