There is an urgent need for an agreement on the principles and key components of antibiotic stewardship to support the EU member states in developing their national or regional programs. A proposal for a conceptual framework was drafted during an international expert workshop on hospital antibiotic stewardship organized under the Czech presidency in Prague on 15 April 2009. This document aims at defining structural and organizational requirements to optimize antibiotic use for hospitalized patients. Optimization should aim at improving patient outcomes, ensuring cost-effective therapy, and reducing the adverse health and ecological effects of antimicrobial use, including drug resistance. Antibiotic stewardship is of relevance to hospital as well as community care. To progress on antibiotic stewardship implementation in the EU, we suggest that three issues need to be addressed: the need for further research on the comparative effectiveness and cost-effectiveness of antibiotic stewardship strategies and interventions in different healthcare settings, the development of expert consensus on key elements of evidence-based best practice in hospital and community antibiotic stewardship, and strengthening the legal basis and core funding of antibiotic stewardship programs as integral components of quality and efficiency of care promotion initiatives.