--- - |2+ Background For decades, economists and sociologists have documented intergenerational transmission of socioeconomic disadvantage, demonstrating that economic, political, and social factors contribute to ‘inherited hardship’. Drawing on biological factors, the developmental origins of adult health and disease model posits that fetal exposure to maternal prenatal distress associated with socioeconomic disadvantage compromises offspring's neurodevelopment, affecting short‐ and long‐term physical and mental health, and thereby psychosocial standing and resources. Increasing evidence suggests that mother‐to‐child influence occurs prenatally, in part via maternal and offspring atypical HPA axis regulation, with negative effects on the maturation of prefrontal and subcortical neural circuits in the offspring. However, even this in utero timeframe may be insufficient to understand biological aspects of the transmission of factors contributing to disadvantage across generations. Methods We review animal studies and emerging human research indicating that parents' childhood experiences may transfer epigenetic marks that could impact the development of their offspring independently of and in interaction with their offspring's perinatal and early childhood direct exposures to stress stemming from socioeconomic disadvantage and adversity. Results Animal models point to epigenetic mechanisms by which traits that could contribute to disadvantage may be transmitted across generations. However, epigenetic pathways of parental childhood experiences influencing child outcomes in the next generation are only beginning to be studied in humans. With a focus on translational research, we point to design features and methodological considerations for human cohort studies to be able to test the intergenerational transmission hypothesis, and we illustrate this with existing longitudinal studies. Conclusions Epigenetic intergenerational transmission, if at play in human populations, could have policy implications in terms of reducing the continuation of disadvantage across generations. Further research is needed to address this gap in the understanding of the perpetuation of compromised lives across generations. - Journal of Child Psychology and Psychiatry, EarlyView.