Carbapenemase producing Enterobacteriaceae (CPE) has emerged as a significant global public health challenge and placing infected patients at risk of potentially untreatable infections. When resistance to carbapenems occurs, there are often few alternative treatments available. Numerous international guidelines have performed systematic and evidence review to identify new strategies to prevent the entry and spread of CPE in healthcare settings. Several key strategies have been shown to be highly effective. Firstly a new strategy that is proven to be effective is the early identification of the CPE carrier patients through active surveillance cultures. While waiting for the screening results, suspected CPE carriers will be put on preemptive isolation in single room and healthcare worker will at the same time practice contact precautions. The active surveillance culture and prompt preemptive isolation will limit the entry and spread of CPE from getting into hospital. Secondly, it is of utmost importance to incorporate enforcement of the basic infection prevention and control best practices in the hospital including, full compliance to hand hygiene, appropriate use of personal protective equipment, execute antibiotic stewardship program to control abuse of antibiotics, effective environmental cleaning and decontamination, staff education and feedback, as well as surveillance of healthcare-associated infections. Such a holistic approach has been shown to be effective in inhibiting CPE from gaining foothold in the hospital.