BACKGROUND: Each year the treatment and care of hundreds of millions of patients worldwide is complicated by infections acquired during healthcare. The impact of healthcare-associated infection may imply prolonged stays in hospital, long-term disability, massive additional financial burden, and deaths. ACTION: Patient safety is a global issue that affects both developed and developing countries. In October 2004, the World Health Organization launched the World Alliance for Patient Safety to co-ordinate and accelerate improvements in patient safety internationally. A core element of the Alliance is the identification of a topic to be addressed as a Global Patient Safety Challenge over a two-year cycle. The first topic chosen for 2005-2006 is healthcare-associated infection. PERSPECTIVES: The Challenge aims at implementing several actions to tackle healthcare-associated infections worldwide, regardless of the level of development of healthcare systems and the availability of resources. Implementation strategies include the integration in different healthcare settings of multiple interventions in the areas of blood safety, injection safety, and clinical procedure safety, as well as water, sanitation, and waste management, with the promotion of hand hygiene in healthcare as the cornerstone.