The long-term consequences of early environmental experiences for development have been explored extensively in animal models to better understand the mechanisms mediating risk of psychopathology in individuals exposed to childhood adversity. One common feature of these models is disruption of the mother-infant relationship which is associated with impairments in stress responsivity and maternal behavior in adult offspring. These behavioral and physiological characteristics are associated with stable changes in gene expression which emerge in infancy and are sustained into adulthood. Recent evidence suggests that these long-term effects may be mediated by epigenetic modification to the promoter regions of steroid receptor genes. In particular, DNA methylation may be critical to maternal effects on gene expression and thus generate phenotypic differentiation of offspring and, through effects on maternal behavior of offspring, mediate the transmission of these effects across generations. In this review we explore evidence for the influence of mother-infant interactions on the epigenome and consider evidence for and the implications of such epigenetic effects for human mental health.