Translational informatics is a rapidly evolving discipline of health informatics that takes advantage of a wide array of methods to acquire data, develop new knowledge, and implement that knowledge to inform healthcare delivery and decisions. Translational informatics has arisen amid a paradigm shift in biomedical informatics, focusing on team-based and user-centered approaches to complex problems spanning traditional organizational boundaries. Work in translational informatics attempts to reduce the delay it takes for discoveries to be made in health care, the time it takes to turn them into practical and useful interventions, and improve their rate of dissemination and implementation. In this chapter, we introduce the term and concept of translational informatics, describe basic frameworks for contextualizing this complex work, and discuss future directions for how translational informatics can improve patient and population health.