Exposure to a traumatic event is required for the diagnosis of posttraumatic stress disorder (PTSD). It was first suggested that PTSD represents a normative response to exposure to extreme stressors, but it soon became evident that only a minority of individuals who experience a traumatic event will develop the disorder. However, the relation between psychopathological events, the phenomenology of the trauma, and neurobiological changes related to PTSD is not totally understood. The symptoms of PTSD are believed to reflect stress-induced changes in neurobiological systems representing an inadequate adaptation of neurobiological systems to exposure to severe stressors. Attempts are made to relate different neurobiological changes to the specific features represented in PTSD. It is not clear whether certain neurobiological changes in PTSD reflect preexisting vulnerability or consequences of trauma exposure. It is known that early life environmental events have persisting effects on central nervous tissue structure and function, a phenomenon called “developmental programming.” Further it is known that glucocorticoid hormone mediators may be involved in this process. It was suggested that changes in the glucocorticoid system are mediated by tissue-specific changes in gene expression. Recent studies suggest that epigenetic mechanisms may play an important role in the interplay between stress exposure and genetic vulnerability. In preclinical studies it was first suggested that epigenetic mechanisms may be involved in the modulation of gene expression in response to stressful stimuli. Recently, epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls were found, indicating the involvement of these mechanisms in human adaptation to stress. Beside DNA methylation, histone modulation is involved in epigenetic regulation of gene expression by regulation of diverse chromatin-templated processes, including transcription. These covalent modifications of histones, including phosphorylation, acetylation, ubiquitination, deimination, and methylation, therefore affect the numerous processes involving chromatin, such as replication, repair, transcription, genome stability and cell death. PTSD may both act as environmental challenges if present in early life and may themselves be more likely in individuals made “vulnerable” by early life stress or even by appearance of PTSD in their parents.