Jointly, the Association for Professionals in Infection Control and Epidemiology (APIC), the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the Association of State and Territorial Health Officials (ASTHO), the Council of State and Territorial Epidemiologists (CSTE), Pediatric Infectious Diseases Society (PIDS), and the Centers for Disease Control and Prevention (CDC) propose a call to action to move toward the elimination of healthcare-associated infections (HAIs) by adapting the concept and plans used for the elimination of other diseases, including infections. Elimination, as defined for other infectious diseases, is the maximal reduction of “the incidence of infection caused by a specific agent in a defined geographical area as a result of deliberate efforts; continued measures to prevent reestablishment of transmission are required.” (p24) This definition has been useful for elimination efforts directed toward polio, tuberculosis, and syphilis and can be readily adapted to HAIs. Sustained elimination of HAIs can be based on this public health model of constant action and vigilance. Elimination will require the implementation of evidence-based practices, the alignment of financial incentives, the closing of knowledge gaps, and the acquisition of information to assess progress and to enable response to emerging threats. These efforts must be under-pinned by substantial research investments, the development of novel prevention tools, improved organizational and personal accountabilities, strong collaboration among a broad coalition of public and private stakeholders, and a clear national will to succeed in this arena.