The developmental outcome of early-life adverse experiences is considered with respect to the interaction between genetic and epigenetic factors. The mechanisms modulating the genome’s responses to environmental signals are illustrated by the discussion of the two genes that play a role in the neurohumoral response to stress, namely the serotonin transporter gene SLC6A4 and the glucocorticoid receptor gene NR3C1. Epigenetic mechanisms are considered as a modulator of these responses providing long-term changes in the phenotype. The reviewed literature highlights the need to combine information on the genome’s structure and its epigenetic status in the analysis of the impact of early-life adverse experience on subsequent development. Such combinatory analyses will also be beneficial for the purposes of personalized diagnosis and therapy of mental disorders.