Optimal early cognitive and emotional development are vital to reaching one’s full potential and represent our best chance to improve the mental health of the population. The developmental origins of health and disease (DOHaD) hypothesis posits that adverse perinatal exposures can alter physiology and increase disease risk. As physiological plasticity decreases with age, interventions applied during gestation may hold the most promise for reducing the impact of mental disorders across the lifespan. However, this vast clinical potential remains largely unrealized as the majority of human DOHaD research is observational in nature. The application of more rigorous experimental designs [e.g. Randomized Controlled Trials (RCTs)] not only represents a major step toward unlocking this potential, but are required to fully test the scientific validity of the DOHaD hypothesis as it pertains to mental illness. Here, we argue that the optimization of maternal diet and exercise during pregnancy represents our best chance to improve offspring neurodevelopment and reduce the burden of mental disorders. Follow-up studies of the offspring of pregnant women enrolled in new and existing RCTs of maternal gestational nutrition+exercise interventions are required to determine if acting during pregnancy can prevent and/or meaningfully reduce the prevalence and severity of mental disorders in the population.