As a term used to denote the ability of defence systems to collaborate, interoperability has emerged as one of the most important capacities of information systems, during the last 30 years. Being important at organizational, process and semantic levels, interoperability soon became a key characteristic of information systems and services, both in the private and public sector. As a crucial prerequisite for automated process execution leading to “one-stop” electronic services and promising dramatic increase in productivity for enterprises of any size, interoperability has been systematically sought after, since the dawn of the 21st century: standardization frameworks, guidelines at enterprise level, data schemas and techniques to tackle the problem of non-communicating systems or organisations started to appear. In parallel, most international software, hardware and service vendors created their own strategies for achieving the goal of open, collaborative, loosely coupled systems and components. This chapter goes beyond the presentation of the main milestones in this fascinating quest for collaboration between people, systems and information: it attempts to describe how this new interdisciplinary research area can transform into a vibrant scientific domain, by applying the necessary method and tools. To achieve that, the chapter presents the ingredients of this new domain, proposes its needed formal and systematic tools, explores its relation with neighbouring scientific domains and finally prescribes the next steps for achieving the thrilling goal of laying the foundations of a new science.