Health care facility water systems have been associated with the transmission of opportunistic premise plumbing pathogens such as Legionella and nontuberculous mycobacteria. These pathogens can enter a building's water system in low numbers and then proliferate when conditions are conducive to their growth. Patients and residents in health care facilities are often at heightened risk for opportunistic infections, and cases and outbreaks in the literature highlight the importance of routine water management programs and occasions for intervention to prevent additional cases. A multidisciplinary proactive approach to water safety is critical for sustained prevention of health care-associated water-related infections.