Hospital-acquired Legionnaires' disease is directly linked to the presence of Legionella in hospital drinking water. Disinfecting the drinking water system is an effective preventive measure. The efficacy of any disinfection measures should be validated in a stepwise fashion from laboratory assessment to a controlled multiple-hospital evaluation over a prolonged period of time. In this review, we evaluate systemic disinfection methods (copper-silver ionization, chlorine dioxide, monochloramine, ultraviolet light, and hyperchlorination), a focal disinfection method (point-of-use filtration), and short-term disinfection methods in outbreak situations (superheat-and-flush with or without hyperchlorination). The infection control practitioner should take the lead in selection of the disinfection system and the vendor. Formal appraisals by other hospitals with experience of the system under consideration is indicated. Routine performance of surveillance cultures of drinking water to detect Legionella and monitoring of disinfectant concentrations are necessary to ensure long-term efficacy.