Hand hygiene is the primary measure to prevent healthcare-associated infections and the spread of antimicrobial resistance. Low staff compliance remains a major problem. Successful promotion requires a multimodal strategy. The World Health Organization (WHO) proposes an approach including at least five components: system change, in particular the recourse to alcohol-based hand rubbing as the new standard of care, staff education using newly developed tools, monitoring and feedback of staff performance, reminders in the workplace, and promotion of an institutional safety climate. Patient participation in hand hygiene promotion is under testing. Early results of the strategy tested in a large number of healthcare settings in both limited- and high-resource countries are extremely encouraging.