Clinical pathways translate evidence-based recommendations into locally practicable, process-specific algorithms that reduce practice variations and optimize quality of care. Our objective was to abstract practice-oriented knowledge from a cohort of real clinical pathways and represent this knowledge as a clinical pathway ontology. We employed a four step methodology: (1) knowledge source identification and classification of clinical pathways according to variations in setting, stage of care, patient type, outcome and specialty; (2) iterative knowledge abstraction using grounded theory; (3) ontology engineering as adapted from the Model-based Incremental Knowledge Engineering approach; and, (4) ontology evaluation through encoding a sample of real clinical pathways. We present our Clinical Pathway Ontology that offers a detailed ontological model describing the structure and function of clinical pathways. Our ontology can potentially integrate with a healthcare semantic web, and ontologies for clinical practice guidelines, patients and institutions to form the foundational knowledge for generating patient-specific CarePlans.