Abstract Population science and disease control researchers can benefit from a more proactive approach to applying bioinformatics tools for clinical and public health research. Bioinformatics utilizes principles of information sciences and technologies to transform vast, diverse, and complex life sciences data into a more coherent format for wider application. Bioinformatics provides the means to collect and process data, enhance data standardization and harmonization for scientific discovery, and merge disparate data sources. Achieving interoperability (i.e. the development of an informatics system that provides access to and use of data from different systems) will facilitate scientific explorations and careers and opportunities for interventions in population health. The National Cancer Institute's (NCI's) interoperable Cancer Biomedical Informatics Grid (caBIG®) is one of a number of illustrative tools in this report that are being mined by population scientists. Tools are not all that is needed for progress. Challenges persist, including a lack of common data standards, proprietary barriers to data access, and difficulties pooling data from studies. Population scientists and informaticists are developing promising and innovative solutions to these barriers. The purpose of this paper is to describe how the application of bioinformatics systems can accelerate population health research across the continuum from prevention to detection, diagnosis, treatment, and outcome.