Hand hygiene is considered to be the most effective measure to prevent microbial pathogen cross-transmission and healthcare-associated infections. In October 2005, the World Health Organization (WHO) World Alliance for Patient Safety launched the first Global Patient Safety Challenge 2005-2006, 'Clean Care is Safer Care', to tackle healthcare-associated infection on a large scale. Within the Challenge framework, international infection control experts and consultative taskforces met to develop new WHO Guidelines on Hand Hygiene in Healthcare. The taskforce was asked to explore aspects underlying hand hygiene behaviour that may influence its promotion among healthcare workers. The dynamics of behavioural change are complex and multi-faceted, but are of vital importance when designing a strategy to improve hand hygiene compliance. A reflection on challenges to be met and areas for future research are also proposed.