Over a century has passed since Ignaz P. Semmelweis demonstrated the association between hand hygiene and nosocomial infections, but this simple procedure is still not recognized by many healthcare workers as one of the most important measures to prevent cross-transmission of microorganisms. A relatively large amount of research has been done, in particular to try to understand why compliance remains so low, in order to implement successful promotion campaigns. This research has generated a fair amount of strong scientific data which are sometimes misunderstood and misused because of myths or certain beliefs. Observational or intervention studies have consistently shown a number of risk factors associated with non-compliance, such as high workload, professional category, or type of ward. Others are thought to be barriers to adequate compliance but have not yet been properly assessed. These include skin irritation due to hand hygiene agents, lack of knowledge of hand hygiene recommendations, or lack of institutional policy. Future interventions to promote hand hygiene will need to address these risk factors, and target the individual healthcare worker, as well as the group or institution if a significant degree of success is to be achieved.