In the near future, genome-wide DNA sequencing will likely become a part of regular medical practice and represents an era of “personalized medicine,” defined by the National Cancer Institute as a “form of medicine that uses information about a person’s own genes or proteins to prevent, diagnose, or treat disease.”1 Genome-wide sequencing (GWS) can be a pathway not only to personalized medicine, but also to population health, which can be defined from a health care delivery perspective as the outcome when a health organization assumes responsibility for the health status of a defined population. Current examples of organizations that assume the responsibility of defined populations include the Veterans Health Administration, Kaiser Permanente, and numerous accountable care organizations. However, while personalized medicine may be a key to population health, the way forward will be costly, wasteful, and potentially harmful without the establishment of priorities, adherence to rules of evidence, and the patience to wait for outcomes to unfold over years of observation.