The increase in the aged population led to a global rise in the demand for elderly healthcare services, such as long-term care facilities (LTCFs), nursing homes, residential homes. Unfortunately, the spread of multidrug-resistant organisms (MDROs) in these structures represent an urgent public health threat requiring immediate action. The aim of this review is to provide a practice guide for the prevention of infections in European LTCFs. A team of experts identify specific problems and proposed practical solutions for the management of colonized and infected patients residing in LTCFs. The heterogeneity of LTCF represents one of the main problems for the implementation of standardized surveillance and infection control programs. Crucial steps involved in the spread of infections among LTCF residents are represented by patient's accommodation, MDRO screening on admission, management of patients with rectal colonization by MDROs, management of patients at high risk of MDRO infections, MDRO transmission by staff and implementation of antimicrobial stewardship. Efforts to implement specific actions in each of these fields are required to reduce the infections in this setting.