Staphylococcus aureus isolates belonging to clonal cluster 398 (CC398) have emerged over the previous decade as a risk to livestock workers. Though most of the research to date has focused on colonization with these strains, a number of infections have also been documented, ranging from mild skin infections to more serious invasive infections and even death. Here, we review existing reports of human infections with CC398 and discuss their geographic distribution, general characteristics, and implications for future research. We identified 74 publications describing CC398 infections in humans in 19 different countries, suggesting this is an emerging worldwide issue.