Family, twin and epidemiological studies all indicate the importance of both genetic as well as environmental risk factor for mood and anxiety disorders, especially unipolar depression and posttraumatic stress disorder (PTSD). In this talk, I will try to illustrate examples of the interplay between genes and stressful early environment for these disorders. I will highlight the identification of potential molecular mechanisms, including allele-specific epigenetics, of such interactions for the glucocorticoid-receptor co-chaperone gene FKBP5 as an example. Finally, I will present data on the potential usefulness of genome-wide expression quantitative trait data and genome-wide DNA methylation data to identify novel targets for gene x environment interaction in stress and trauma-related psychiatric disorders.