Based on the paradigm changes for health, health services and underlying technologies as well as the need for at best comprehensive and increasingly automated interoperability, the paper addresses the challenge of knowledge representation and management for medical decision support. After introducing related definitions, a system-theoretical, architecture-centric approach to decision support systems (DSSs) and appropriate ways for representing them using systems of ontologies is given. Finally, existing and emerging knowledge representation and management standards are presented. The paper focuses on the knowledge representation and management part of DSSs, excluding the reasoning part from consideration.