Genetics, epigenetics, infection, stress and trauma predispose individuals to systemic chronic inflammation that contributes to mental illness, autoimmune conditions, and chronic disease. This paper explores the interplay of these issues and their serious health consequences. While modern medicine has made significant advances in disease care, it appears that lifestyle intervention, early childhood intervention, and socioeconomic investment and have the potential to make an even greater impact on the mental and physical well-being of the population.