Many healthcare organizations, professional associations, government and accrediting agencies, legislators, regulators, payers, and consumer advocacy groups have advanced the prevention of healthcare-associated infections as a national imperative, stimulating the creation of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in this supplement. In this introduction, we provide background and context and discuss the major issues that shaped the recommendations included in the compendium.