Interest in application programming interfaces (APIs) as a means to increase health data access and exchange among patients, health care providers, and payers has become an important area for development. In an effort to better understand the various contexts in which APIs can be applied, we explored different use cases. While APIs and our collective understanding of the best ways to implement and use them continue to develop, in the coming years the use of proprietary and standards-based APIs could be key to the sustainability of applied clinical informatics research, as well as associated improvements in patient engagement, clinical decision making, efficiency, quality and safety of the healthcare delivery system.