Objectives: To meet the challenge for high quality and efficient care, highly specialized and distributed healthcare establishments have to communicate and co-operate in a semantically interoperable way. Information and communication technology must be open, flexible, scalable, knowledge-based and service-oriented as well as secure and safe. Methods: For enabling semantic interoperability, a unified process for defining and implementing the architecture, i.e. structure and functions of the co-operating systems' components, as well as the approach for knowledge representation, i.e. the used information and its interpretation, algorithms, etc. have to be defined in a harmonized way. Deploying the Generic Component Model, systems and their components, underlying concepts and applied constraints must be formally modeled, strictly separating platform-independent from platform-specific models. Results: As HL7 Version 3 claims to represent the most successful standard for semantic interoperability. HL7 has been analyzed regarding the requirements for model-driven, service-oriented design of semantic interoperable information systems, thereby moving from a communication to an architecture paradigm. The approach is compared with advanced architectural approaches for information systems such as OMG's CORBA 3 or EHR systems such as GEHR/openEHR and CEN EN 13606 Electronic Health Record Communication. Conclusion: HL7 Version 3 is maturing towards an architectural approach for semantic interoperability. Despite current differences, there is a close collaboration between the teams involved guaranteeing a convergence between competing approaches.