In this review, Karam and Heffner address a common problem in the ICU: the emergence of infections by multidrug-resistant pathogens. The first part of the article is a general appraisal of antibiotic resistance acquisition and prevention strategies. In the second part, the authors discuss the treatment of Gram-negative bacilli infections, which is now determined by the generation of β-lactamases, as follows: type 1 (with resistance to several β-lactams) or non-type 1 (with resistance not only to β-lactams). The authors then consider enterococcal infections, in particular vancomycin-resistant strains of pathogens. These infections provide an example of an infection that spreads rapidly under favorable conditions (eg, very high use of vancomycin in ICUs). In fact, the recommended approach is the reduction of vancomycin use. Finally, Karam and Heffner discuss Candida infections, which are now an emerging threat, especially because of the shift toward infections with species other than Candida albicans. The problem with Candida isolation in nonsterile products is establishing their pathogenic role.