This paper reports findings from a study aimed at demonstrating the importance of hand hygiene in healthcare settings as the most effective preventive measure against healthcareassociated infections (HAIs) as part of the National Concept for the Prevention of Healthcare-Associated Infections (approved by Chief Public Health Officer of Russia, November 6, 2011). Currently, healthcare-associated infections (HAIs) remain a serious challenge to Russian healthcare. Poor infection control in healthcare settings and overuse of antimicrobials have been identified as major contributors to HAIs. The research methods such as content analysis, literature review, ranking, hypothetico-deductive method, generalization, and formalization were used. This study was conducted using international bibliographic and abstract databases (Scopus, PubMed); Russian public documents, and international regulations (legal acts, programs, conventions, etc.) focused on healthcare-acquired infections. The systematic literature review suggests that one of the most effective measures to prevent HAIs is hand hygiene. A multimodal approach has been found to be an effective tool to maximize the prevention of HAIs. The available scientific researches identify the 5 key moments of hand hygiene, a concept explaining when healthcare workers (HCWs) should perform hand hygiene. It was concluded that HAIs prevention should be based on multifaceted strategies. In this context HAIs are successfully preventable through changing hospital culture, and well-coordinated efforts at the national level are essential to control HAIs which may pose a significant threat.