The prevalence of multidrug-resistant pathogens, especially in intensive care units, has increased and represents a great concern for medical and scientific community. Infections caused by these pathogens are associated with increased costs, length of hospitalization, and morbidity/mortality rates. The last decade was marked by the spread of carbapenem resistance determinants especially in Enterobacteriaceae isolates. In this review, the Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae is used as an example to discuss the difficulties in dealing with multidrug-resistant pathogens in the intensive care unit setting and how they represent a challenge to the medical-scientific community and, ultimately, the whole society.