Epigenetics, the study of non-DNA sequence−related heredity, is at the epicenter of modern medicine because it can help to explain the relationship between an individual's genetic background, the environment, aging, and disease. It can do so because the epigenetic state varies among tissues and during a lifetime, whereas the DNA sequence remains essentially the same. As cells adapt to a changing internal and external environment, epigenetic mechanisms can remember these changes in the normal programming and reprogramming of gene activity. The common disease genetic and epigenetic (CDGE) model provides an epidemiologic framework that can incorporate epigenetic with genetic variation in the context of age-related susceptibility to disease. Under CDGE, the epigenetic program can modify the effects of deleterious genes or may be influenced by an adverse environment. Thus, including epigenetics into epidemiologic studies of human disease may help explain the relationship between the genome and the environment and may provide new clues to modifying these effects in disease prevention and therapy.