Interoperability is the ability of two or more systems, devices, or organizations to connect and exchange data. Effective interoperable systems understand and accurately interpret the exchanged information with minimal human intervention. As patients are mobile and seek medical care at different health systems, interoperability is a fundamental capability needed to ensure vital healthcare information is available to the medical team  to support their decision-making and coordination. Interoperability is built upon shared standards for different types of healthcare data. This chapter will review the history of interoperability, establish relevant definitions, and explore the applications and impact of interoperability on healthcare. It will also discuss significant challenges in the implementation and use of interoperability, including standardization, data security, and logistical hurdles. By the end of the chapter, the reader will understand the pivotal role interoperability plays in the modern healthcare ecosystem.