Software systems are increasingly composed of independently-developed components, which are often systems by their own. This composition is possible only if the components are interoperable, i.e., are able to work together in order to achieve some user task(s). However, interoperability is often hampered by the differences in the data types, communication protocols, and middleware technologies used by the components involved. In order to enable components to interoperate despite these differences, mediators that perform the necessary data translations and coordinate the components' behaviours appropriately, have been introduced. Still, interoperability remains a critical challenge for today's and even more tomorrow's distributed systems that are highly heterogeneous and dynamic. This chapter introduces the fundamental principles and solutions underlaying interoperability in software systems with a special focus on protocols. First, we take a software architecture perspective and present the fundamentals for reasoning about interoperability and bring out mediators as a key solution to achieve protocol interoperability. Then, we review the solutions proposed for the implementation, synthesis, and dynamic deployment of mediators. We show how these solutions still fall short in automatically solving the interoperability problem in the context of systems of systems. This leads us to present the solution elaborated in the context of the European Connect project, which revolves around the notion of emergent middleware, whereby mediators are synthesised on the fly.