The 'All of Us' Research Program is an ambitious and innovative initiative that requires flexibility in the way participants are approached, enrolled and engaged. A one-size-fits-all may not work for an initiative that strives to recruit a large representative sample of the U.S. population, as participant cultural and other differences may require adaptation to support inclusivity. Authorized individuals from any institution will be able to access this valuable resource, and the value proposition for participating institutions relies on a shared vision of how All of Us will advance Research and improve health. We assembled a multidisciplinary team of Regional Medical Centers (RMCs) in a large Consortium of organizations in California. The All of Us California Precision Medicine Consortium (CAPMC) epitomizes All of Us: (1) we have a large base from which to recruit participants in a state that is committed to enhancing high quality Research, and scientific excellence leading to generalizability of findings; (2) the populations in our catchment areas are among the most diverse in the world; and (3) we believe that All of Us’s intent to provide health data, risk assessment for particular conditions, and tools for participants, citizen scientists, and Researchers to make simple queries and obtain aggregate results in a privacy-preserving manner is critical to the advancement of science.