Stress affects the risk for psychiatric illnesses. Emerging research shows that stress not only alters disease risk within the lifetime of an individual but also modifies molecular and behavioral responses across generations. As familial predisposition can only in part be explained by genetic factors for the majority of psychiatric ailments, epigenetics is a promising candidate for intergenerational stress effects. Here, we provide evidence from animal models and human studies for the epigenetic inheritance of stress effects. In this chapter, we discuss factors that may contribute to the controversy of this novel research field, including the importance of critical periods, stressor type, and other nongenetic modes of transmission. Although currently human studies on epigenetic inheritance are rare, more research in this field will advance our understanding of human disease and may provide a new dimension to personalized therapy.