With increasing availability of clinical data in machine-readable form, and decreasing cost of storing and manipulating that data, retrospective research using clinical databases has become more feasible. Nonetheless, much of the potential for clinical research using these data remains unrealized. Obstacles to clinical database research include difficulty accessing data, difficulty using retrospective data to draw valid inferences about medical tests and treatments, and a shortage of investigators trained and interested in using a clinical database to answer their questions. At the University of California, San Francisco, we have developed a Clinical Database Research Program (CDRP) to try to overcome these obstacles. The CDRP maintains a relational database of patient data obtained from diverse sources and a small staff dedicated to providing such data to researchers. The CDRP staff also provides support for design and analysis of studies using the database-the development of methods for such studies is our primary research interest. Finally, to increase the number of investigators using the database for research, we are integrating training in clinical epidemiology and clinical research methods into residency and fellowship training, and offering an elective in clinical database research for trainees who wish to undertake a specific project.