Although healthcare-acquired infections have received wide spread attention from hospitals, healthcare associations, and regulators, they remain a serious patient care issue and an avoidable high expense. The 2010 goal set by the Centers for Medicare & Medicaid Services to decrease HAIs by 40% by 2013—which would result in 1.8 million fewer injuries to patients—was not met. Starting October 1, 2014, hospitals with the highest rates of preventable HAIs will be penalized 1%, adding to existing federal penalties. Hospitals and health systems can invest in educating clinicians and cleaning staffs, enforcing proven measures such as hand washing, and installing systems to monitor rates following interventions. Yet HAI prevention and treatment depends less on procedures and more on culture, leadership, and organizational commitment, say five healthcare leaders who recently joined with HealthLeaders Media for an in-depth, three-hour conversation.