The functional development and maturation of the brain and behaviour are based on a complex, coordinated interaction between genetic predispositions and environmental influences. Stressful experiences or trauma in early life can negatively interfere with these developmental processes and, as a result, impair brain function, especially in prefrontal-limbic areas that are implicated in the regulation of stress response and socio-emotional behaviour. Perinatal stress, therefore, represents a significant risk factor for the development of mental disorders, such as depression, anxiety disorders or ADHD. It is important to emphasize that the described effects often occur in a sex-specific manner. However, successful coping with early negative experiences can also lead to positive adaptive changes in neural structures, which may improve stress coping and, thus, promote resilience in later life. There is considerable evidence that the interaction between genetic predispositions and the programming influences of early-life stress (ELS) on brain development is mediated by epigenetic mechanisms. A growing number of studies also show that the stress-induced, epigenetically regulated changes in brain function and behaviour can be passed on to subsequent generations in the sense of an inter- or transgenerational epigenetic inheritance. Thus, early-life stress not only affects the directly exposed individual but also represents a transgenerational programming factor that determines an epigenetic predisposition for the development of an individual in subsequent generations. This chapter summarizes major findings with respect to the environmentally driven development of functional brain circuits and their underlying epigenetic mechanisms and also discusses the potential, epigenetically mediated, inter- and transgenerational transmission of stress-induced neuronal and behavioural adaptations.