Healthcare-associated infections (HCAIs) are a major source of morbidity and mortality and are the second most prevalent cause of death. Furthermore, it has been reported that for every one-hundred patients admitted to hospital, seven patients in high-income economies and ten in emerging and low-income economies acquire at least one type of HCAI. Currently, almost all pathogenic microorganisms have developed antimicrobial resistance, and few new antimicrobials are being developed and brought to market. The literature search for this narrative review was performed by searching bibliographic databases (including Google Scholar and PubMed) using the search terms: "Strategies," "Prevention," and "Healthcare-Associated Infections," followed by snowballing references cited by critical articles. We found that although hand hygiene is a centuries-old concept, it is still the primary strategy used around the world to prevent HCAIs. It forms one of a bundle of approaches used to clean and maintain a safe hospital environment and to stop the transmission of contagious and infectious microorganisms, including multidrug-resistant microbes. Finally, antibiotic stewardship also has a crucial role in reducing the impact of HCAIs through conserving currently available antimicrobials.