Hand hygiene is the most effective measure to prevent cross-transmission of microorganisms. Adequate hand hygiene can be achieved by standard handwashing--with water alone or with soap--or by the use of an alcohol-based hand-rub solution. Despite considerable efforts, compliance with this simple infection-control measure remains low. Factors predicting non-compliance have been extensively studied, and include physician status, procedures associated with a high risk of cross-transmission, and an important workload. Future interventions to improve compliance should consider complex behavioral theories and the use of multimodal and multidisciplinary strategies. We believe that one of the key components of these interventions should be the wide use of alcohol-based hand-rub, which is microbiologically effective and less time-consuming than standard handwashing.