Enterobacteriaceae are a family of bacteria that commonly cause infections in health-care settings as well as in the community. Among Enterobacteriaceae, resistance to broad-spectrum carbapenem antimicrobials has been uncommon. Over the past decade, however, carbapenem-resistant Enterobacteriaceae (CRE) have been recognized in health-care settings as a cause of difficult-to-treat infections associated with high mortality.The percentage of acute-care hospitals reporting at least one CRE from health-care-associated infections (HAIs) in 2012 was estimated using data submitted to the National Healthcare Safety Network (NHSN) in 2012. The proportion of Enterobacteriaceae infections that were CRE was calculated using two surveillance systems: 1) the National Nosocomial Infection Surveillance system (NNIS) and NHSN (for 2001 and 2011, respectively) and 2) the Surveillance Network-USA (TSN) (for 2001 and 2010). Characteristics of CRE culture-positive episodes were determined using data collected as part of a population-based CRE surveillance project conducted by the Emerging Infections Program (EIP) in three states.In 2012, 4.6% of acute-care hospitals reported at least one CRE HAI (short-stay hospitals, 3.9%; long-term acute-care hospitals, 17.8%). The proportion of Enterobacteriaceae that were CRE increased from 1.2% in 2001 to 4.2% in 2011 in NNIS/NHSN and from 0% in 2001 to 1.4% in 2010 in TSN; most of the increase was observed in Klebsiella species (from 1.6% to 10.4% in NNIS/NHSN). In the EIP surveillance, 92% of CRE episodes occurred in patients with substantial health-care exposures.Carbapenem resistance among common Enterobacteriaceae has increased over the past decade; most CRE are associated with health-care exposures.Interventions exist that could slow the dissemination of CRE. Health departments are well positioned to play a leading role in prevention efforts by assisting with surveillance, situational awareness, and coordinating prevention efforts.