Over the past 10 years, dissemination of Klebsiella pneumoniae carbapenemase (KPC) has led to an increase in the prevalence of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. Infections caused by CRE have limited treatment options and have been associated with high mortality rates. In the previous year, other carbapenemase subtypes, including New Delhi metallo-β-lactamase, have been identified among Enterobacteriaceae in the United States. Like KPC, these enzymes are frequently found on mobile genetic elements and have the potential to spread widely. As a result, preventing both CRE transmission and CRE infections have become important public health objectives. This review describes the current epidemiology of CRE in the United States and highlights important prevention strategies.