The articles included in this special issue of Families, Systems, & Health on informatics represent distinct elements of health informatics relevant to the implementation and provision of clinical services. Informatics is the collection, analysis, and application of data for direct care decisions in health care and an interdisciplinary field that brings medicine together with computer, cognitive, and social sciences. We frame the contributions of the included articles within the framework of the Quadruple Aim for health care: better outcomes, lower costs, improved patient satisfaction, and improved work life of health care providers. The examples provided aim to show how health informatics provides opportunities to improve care delivered to patients at individual and system levels while both identifying and closing gaps in research addressing the management and use of information generated in the course of delivering health care. The articles in this special issue reflect the cutting edge of health care, research and technology, where there is as much risk as there is promise of delivering stability to our dynamic health care system.