AbstractThe genome is programmed by the epigenome. Two of the fundamental components of the epigenome are chromatin structure and covalent modification of the DNA molecule itself by methylation. DNA methylation patterns are sculpted during development and it has been a long held belief that they remain stable after birth in somatic tissues. Recent data suggest that DNA methylation is dynamic later in life in postmitotic cells such as neurons and thus potentially responsive to different environmental stimuli throughout life. We hypothesize a mechanism linking the social environment early in life and long‐term epigenetic programming of behavior and responsiveness to stress and health status later in life. We will also discuss the prospect that the epigenetic equilibrium remains responsive throughout life and that therefore environmental triggers could play a role in generating interindividual differences in human behavior later in life. We speculate that exposures to different environmental toxins alters long‐established epigenetic programs in the brain as well as other tissues leading to late‐onset disease. Environ. Mol. Mutagen., 2008. © 2007 Wiley‐Liss, Inc.