Clinical decision intelligence (CDI) is an emerging area in health care, covering a broad range of subjects, from clinical data integration and data analysis to knowledge management and application development. The goal of CDI systems is to improve health-care quality and reduce costs through the discovery, management, and application of clinical intelligence from heterogeneous and rapidly expanding data sources. These sources include data from clinical practice, nursing, health-care management, health-care administration, and medical research. In this paper, we discuss the functional requirements and reference architecture for CDI systems and their clinical applications. This architecture includes an integrated framework for managing the entire CDI process, a standardized enterprise ontology management system, and a clinical knowledge representation platform. The CDI approach has the potential to transform the health-care management process through the integration of business intelligence, business rule management, and business process management in a clinical setting, and to help health-care organizations move closer to an on demand model.