Lately, there have been considerable efforts to computerize Clinical Practice Guidelines (CPG) so that they can be executed via Clinical Decision Support Systems (CDSS) at the point of care. We present a Semantic Web framework to both model and execute the knowledge within a CPG to develop knowledge-centric CDSS. Our approach entails knowledge modeling through a synergy between multiple ontologies–i.e. a domain ontology, CPG ontology and patient ontology. We develop decision-rules based on the ontologies, and execute them with a proof engine to derive CPG-based patient specific recommendations. We present a prototype of our CPG-based CDSS to execute the CPG for Follow-up after Treatment for Breast Cancer.