Hand hygiene, either by hand disinfection or hand washing remains to be most pivotal in controlling infection in healthcare settings. Hand hygiene is a simple practice that has been at the core of infection prevention for over 150 years. Yet getting healthcare personnel to follow recommended hand hygiene practices in today’s complex and demanding healthcare environment continues to be a monumental challenge. Even in the developed world, adherence is estimated to be less than 50%, meaning healthcare personnel practice hand hygiene fewer than half of the times that they should. Health care associated infections are drawing increasing attention from patients, insurers, governments and regulatory bodies. This is not only because of the magnitude of the problem in terms of the associated morbidity, mortality and cost of treatment, but also due to the growing recognition that most of these are preventable. The medical community is witnessing in tandem unprecedented advancements in the understanding of pathophysiology of infectious diseases and the global spread of multi-drug resistant infections in health care set-ups. These factors, compounded by the paucity of availability of new antimicrobials have necessitated a re-look into the role of basic practices of infection prevention in modern day health care. There is now undisputed evidence that strict adherence to hand hygiene reduces the risk of cross-transmission of infections. Simple preventive measures have been proven effective to contain infections. An advanced level of hand hygiene program with elements of infection control should be offered to the all the professionals working in healthcare setting. Cultural and behavioural issues would play in role in low compliance despite of the efforts to improve quality of healthcare. This review focuses on one of the simplest, low cost but least accepted tool in infection prevention.