Healthcare-associated infection is a major safety issue affecting the quality of care of hundreds of millions of patients every year in both developed and developing countries. To meet the goal of ensuring patient safety across healthcare settings around the globe, the World Health Organization launched the World Alliance for Patient Safety in October 2004. Healthcare-associated infections were identified as a fundamental work priority and selected as the topic of the First Global Patient Safety Challenge launched by the Alliance. Under the banner "Clean Care is Safer Care", the Challenge aims at implementing several actions to reduce healthcare-associated infections worldwide, regardless of the level of development of healthcare systems and the availability of resources. Implementation strategies include the integration of multiple interventions in the areas of blood safety, injection safety, clinical procedure safety, and water, sanitation and waste management, with the promotion of hand hygiene in healthcare as the cornerstone. Several initiatives have been undertaken to raise global awareness and to obtain country commitment to support action on this issue. The new Guidelines on Hand Hygiene in Health Care, including the most consistent scientific evidence available, have been issued in an advanced draft form. An implementation strategy is proposed therein to provide solutions to overcome obstacles to improvement in compliance with hand hygiene practices, together with a range of practical tools for use in healthcare settings. The latter are currently undergoing testing in several pilot sites to evaluate feasibility, acceptability and sustainability.