Informatics for Integrating Biology and the Bedside (I2B2) addresses one of the central bottlenecks in translating findings and hypotheses in model systems or organisms into studies and findings relevant to improving human health: the difficulty in conducting clinical research that makes use of all the possibilities afforded by the full array of new information provided by genomic research. I2B2's scalable computational and organizational framework for conducting clinical research in and across large multidisciplinary academic medical centers is designed for the establishment of a "new" biomedicine that both (a) fully exploits the fruit of the genomic revolution for clinical practice and (b) allows clinical care to be leveraged to advance basic biological research. We have chosen as our laboratory the entirety of a leading, large academic healthcare system: Partners Healthcare as well as other hospitals affiliated with Harvard Medical School. Among our investigators are the leaders in information technology, clinical research, biological research and genomic research at these hospitals. We have adopted collaborative and administrative structures based on decade long histories of multi-disciplinary research, notably at the Division of Health Sciences and Technology of Harvard and MIT. These are matched with Driving Biology Projects championed by leading clinical researchers in diabetes mellitus, neurological disease, airways disease and hypertension brought together for the first time by these structures and opportunities. The models of collaboration as well as the tools, computational methodologies and educational programs will be widely disseminated through the I2B2 dissemination core and through specifically targeted programs for underrepresented minorities.