Human fetal regulatory systems are highly sensitive to maternal stress, toxins, nutritional deprivation, maternal infection, and inflammation. The developmental origins of health and disease (DOHaD) hypothesis posits that fetal adaptation to stressful intrauterine conditions may alter organ development and function, increasing the risk for disease later in life. Adverse intrauterine conditions are reflected in shortened gestation, smaller body size at birth, and, in some cases, fetal growth restriction as well. Extremely preterm birth is a complex, multi-faceted risk factor that may warrant significant management across the lifespan. As adults, survivors continue to face significant physiological and psychological stresses that affect their health, education, mobility, work, and social functioning. In the present chapter, we compare long-term functional outcomes in adult survivors of extremely low birth weight (ELBW; ≤1000 g) and adults born at normal birth weight (NBW; ≥2500 g) in the McMaster ELBW Cohort, the oldest known prospectively followed cohort of ELBW survivors, born from 1977 to 1982. While some consequences of these early stresses are not subject to mitigation, strategies exist to manage their long-term effects. We examine naturalistic and structural models of acquired resilience that may reduce the impact of stressors associated with extremely preterm birth.