While society would benefit from a reduced incidence of nosocomial infections, there is currently no direct reimbursement to hospitals for the purpose of infection control, which forces healthcare institutions to make economic decisions about funding infection control activities. Demonstrating value to administrators is an increasingly important function of the hospital epidemiologist because healthcare executives are faced with many demands and shrinking budgets. Aware of the difficulties that face local infection control programs, the Society for Healthcare Epidemiology of America (SHEA) Board of Directors appointed a task force to draft this evidence-based guideline to assist hospital epidemiologists in justifying and expanding their programs. In Part 1, we describe the basic steps needed to complete a business-case analysis for an individual institution. A case study based on a representative infection control intervention is provided. In Part 2, we review important basic economic concepts and describe approaches that can be used to assess the financial impact of infection prevention, surveillance, and control interventions, as well as the attributable costs of specific healthcare-associated infections. Both parts of the guideline aim to provide the hospital epidemiologist, infection control professional, administrator, and researcher with the tools necessary to complete a thorough business-case analysis and to undertake an outcome study of a nosocomial infection or an infection control intervention.