Multidrug-resistant organism (MDRO) outbreaks have been steadily increasing in intensive care units (ICUs). Still, healthcare institutions and workers (HCWs) have not reached unanimity on how and when to implement infection prevention and control (IPC) strategies. We aimed to provide a pragmatic physician practice-oriented resume of strategies towards different MDRO outbreaks in ICUs. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios; education, isolation, decolonization, screening, and hygiene practices; outbreak reporting; cost-effectiveness; reproduction numbers (R); and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician lose sight of the big picture. IPC strategies have proven their cost-effectiveness regardless of typology, country, and pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, the elaboration of a rapid outbreak recognition tool (i.e., an easy-to-use mathematical model) would improve early diagnosis and prevent spreading. Further studies are needed to express views in favor or against MDRO decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategy application has made and still makes ICUs major MDRO reservoirs in the community. In a not-too-distant future, genetic engineering and phage therapies could represent a plot twist in MDRO IPC strategies.