Healthcare-associated infection affects hundreds of millions of people worldwide and is a major global issue for patient safety. It complicates between 5 and 10% of admissions in acute care hospitals in industrialised countries. In developing countries, the risk is two to twenty times higher and the proportion of infected patients frequently exceeds 25%. A growing awareness of this problem prompted the World Health Organization to promote the creation of the World Alliance for Patient Safety. Prevention of healthcare-associated infection is the target of the Alliance First Global Patient Safety Challenge, 'Clean Care is Safer Care', launched in October 2005. After 2 years, a formal statement has been signed by 72 ministries of health as a pledge of their support to implement actions to reduce healthcare-associated infection; of these, 30 are developing countries. Additional countries, mostly from the developing world, have planned to sign by the end of 2008 and will represent in total more than three-quarters of the world's population. Given the emphasis of the proposed strategy on simple and affordable solutions, the impact of the Challenge is expected to be high in developing countries. The combined efforts expected under the Challenge have the potential to save millions of lives, prevent morbidities and long-term disability for hundreds of millions of patients, and lead to major cost savings through the improvement of basic infection control measures in any healthcare setting, regardless of resources available or level of development.