The NIH mission is “to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” NIH-funded research is structured to address the major diseases driving morbidity and mortality. Interrogating and developing therapeutics for one disease at a time has often been productive. Will, however, the success of this approach be sustainable for the chronic aging diseases, such as neurodegenerative and metabolic syndromes, most cancers, and cardiovascular disease? Findings in the last few decades have made it impossible to ignore the integrative nature of human physiology. Pathologies thought to be disparate are now understood to be connected. This awareness raises the possibility that the stated goals in the NIH mission statement are best achieved by novel integrated approaches to health and disease, with the understanding that biological systems change with age.