Stress and adversity experienced during early development can exert a profound and persistent imprint on our physiology, brain, and health across the lifespan. This imprint can lead to long-term health outcomes ranging from substance use and depression to obesity and cardiovascular disease. There is also emerging evidence that stress and adversity may be transmitted from one generation to the next. However, protective experiences may prevent or mitigate these effects. This lecture will provide examples of findings from Dr. Stroud’s laboratory focused on revealing the earliest intergenerational transmission of maternal experiences and behaviors (particularly substance use) in fetuses and babies; the importance of understanding and intervening during sensitive periods; and the need for understanding the broader “exposome” including social and structural impacts.