There is an increased level of activity in the biomedical and health informatics world (e-prescribing, electronic health records, personal health records) that, in the near future, will yield a wealth of available data that we can exploit meaningfully to strengthen knowledge building and evidence creation, and ultimately improve clinical and preventive care. The American Medical Informatics Association (AMIA) 2008 Health Policy Conference was convened to focus and propel discussions about informatics-enabled evidence-based care, clinical research, and knowledge management. Conference participants explored the potential of informatics tools and technologies to improve the evidence base on which providers and patients can draw to diagnose and treat health problems. The paper presents a model of an evidence continuum that is dynamic, collaborative, and powered by health informatics technologies. The conference's findings are described, and recommendations on terminology harmonization, facilitation of the evidence continuum in a "wired" world, development and dissemination of clinical practice guidelines and other knowledge support strategies, and the role of diverse stakeholders in the generation and adoption of evidence are presented.