Inappropriate antibiotic use and antibiotic resistance are now major global issues. Antimicrobial stewardship programmes are increasingly being used to optimize antibiotic prescribing in acute care. The central tenet of these programmes tends to be policy and guidelines aimed at prescribers. However, rules and guidelines alone may not be sufficient to bring about effective and sustainable optimization of practice. Best practice needs to be positively reinforced by an environment that facilitates and supports optimal prescribing choices, i.e. a 'choice architecture' that makes prudent antibiotic prescribing the path of least resistance. To make prudent antibiotic management an integral part of the behaviour of all healthcare professionals and to bring about quality improvement it is necessary to adopt a whole-system approach. To do this it is necessary first to understand the factors that influence antibiotic management and prescribing.