Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant organisms with few treatment options that cause infections associated with substantial morbidity and mortality. CRE outbreaks have been increasingly reported worldwide and are mainly due to the emergence and spread of strains that produce carbapenemases. In the United States, transmission of CRE is primarily driven by the spread of organisms carrying the Klebsiella pneumoniae carbapenemase enzyme, but other carbapenemase enzymes, such as the New-Delhi metallo-β-lactamase, have also emerged. Currently recommended control strategies for healthcare facilities include the detection of patients infected or colonized with CRE and implementation of measures to prevent further spread. In addition to efforts in individual facilities, effective CRE control requires coordination across all healthcare facilities in a region. This review describes the current epidemiology and surveillance of CRE in the United States and the recommended approach to prevention.