Precision Medicine in Chronic Disease – using genetics and personalized medical nutrition to activate underperforming mechanisms in disease. As of 2020 157 million Americans are living with at least 1 chronic condition, with 81 million having multiple chronic conditions. Concurrently it is understood that epigenetics partnered with genetics play a large part in this, with the epigenetic factors largely within our control. With the advent of inexpensive access to the genome and the increasing understanding of personalization in medicine, the time is ripe for creating a foundational, personalized approach to chronic disease. The inflammatory mechanisms that underlie all disease are understood – autophagy/mtor, oxidative stress response, NAD+pathways, etc. These pathways are genetically driven and combine to impact the cell danger response. These mechanisms are first-line factors and create the environment that surrounds our genetic predisposition to disease, as well as our epigenetic influences. Nutritional factors are in fact the prime movers of these mechanisms, suggesting that a patient’s ability to transform nutritional factors significantly impacts chronic disease avoidance and/or resolution. Targeting these mechanisms through personalized medical nutrition can positively impact pathway function an the foundation for chronic disease avoidance/resolution.