OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on family history and improving health. PARTICIPANTS: A non-DHHS, nonadvocate 16-member panel representing the fields of family medicine, population health, pediatrics, obstetrics and gynecology, health economics, epidemiology, biostatistics, medical genetics, nursing, endocrinology, behavioral science, ethics, health services and outcomes research, and a public representative. In addition, 21 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the McMaster University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: The panel recognized that family history has an important role in the practice of medicine and may motivate positive lifestyle changes, enhance individual empowerment, and influence clinical interventions. The panel found that it is unclear how this information can be effectively gathered and used in the primary care setting for common diseases. The emerging international paradigm on using evidence-based methods to evaluate tests and interventions works best when one can trace a linear pathway from test development through randomized controlled trials that anchor usefulness in clinical practice with quantitative evidence of benefits and harms (principles best exemplified in the field of genetics by the ACCE and Evaluation of Genomic Applications in Practice and Prevention methodologies). Family history was a core element of clinical care long before the evidence-based medicine paradigm was even proposed. Therefore, it comes as no surprise that the evidence base supporting family history for common diseases in primary care, as assessed in this state-of-the-science review, is weak in defining the key elements, assessing test performance, linking results to clinical conditions, acting on results in specific clinical scenarios, evaluating potential benefits and harms, and assessing factors encouraging and discouraging use of family history. For a systematically collected family history for common diseases to become an evidence-based tool in primary care clinical settings, substantial additional research will be needed. Challenges include the number, complexity, and cost of rigorous studies that have potential to adequately address the scientific questions outlined in this panel's research recommendations. The relative priority of specific research questions on family history in the context of other health information and genetic technologies and interventions that might address the same clinical problems in different ways requires debate in order to ensure the best outcomes for improving health.