Quality and performance improvement initiatives are driving significant changes in the United States healthcare system. In anticipation of the full implementation of national health reform over the next several years, the pace of these changes has been increasing. The goals of these quality initiatives mirror the National Quality Strategy's three aims which developed out of the Institute for Healthcare Improvement’s triple aim of improving the patient care experience, improving the population’s health, and reducing healthcare costs. Projects are underway across the United States to achieve these aims. In this article, Chief Nursing Officers of three of the nation’s largest healthcare systems, the Department of Veterans Affairs, Kaiser Permanente, and Ascension Health, have outlined their organizations’ quality and performance improvement initiatives. Their forward-thinking projects broadly address several aspects of healthcare, including reduction of hospital-acquired conditions, patient engagement, and the integration of mobile technologies and other informatics solutions to improve clinical workflows and increase registered nurses’ access to knowledge resources. The article then offers a brief analysis and conclusion of these three exemplars. The projects span the information systems life cycle: some are well established and continuing to improve, others have been recently implemented, and still others planned for implementation in the near future.