There is a critical gap in our nation's ability to accurately measure and manage the quality of medical care. A robust healthcare quality information system (HQIS) has the potential to address this deficiency through the capture, codification, and analysis of information about patient treatments and related outcomes. Because non-technical issues often present the greatest challenges, this paper provides an overview of these socio-technical issues in building a successful HQIS, including the human, organizational, and knowledge management (KM) perspectives. Through an extensive literature review and direct experience in building a practical HQIS (the National Comprehensive Cancer Network Outcomes Research Database system), we have formulated an "informatics blueprint" to guide the development of such systems. While the blueprint was developed to facilitate healthcare quality information collection, management, analysis, and reporting, the concepts and advice provided may be extensible to the development of other types of clinical research information systems.