This chapter discusses the impact of health care‐associated infections (HAIs) on patient outcomes and health care costs and the organization of the hospital infection prevention program (IPP) and describes the important role that the clinical microbiology laboratory (CML) plays in HAI prevention. An HAI is an infection that is acquired in a hospital or health care facility. The incidence of HAIs involving staphylococci and enterococci increased as these organisms became increasingly resistant to antibiotics. The responsibilities of the hospital IPP include surveillance and prevention of HAIs, continuing education of medical staff, outbreak control, protection of employees and visitors from infection, and providing advice on introduction of new products and procedures. The development and application of new technologies in the CML can greatly enhance infection prevention efforts. Close collaboration between CML and personnel from infection prevention and antimicrobial stewardship programs is required to ensure optimal HAI prevention, which saves money and lives.