Evidence from both human and preclinical studies seems to indicate that maternal smoking, alcohol drinking, or other drug use during pregnancy can affect offspring outcomes. It also suggests that maternal substance use during pregnancy is a major preventable cause of adverse infant outcomes. Nonetheless, more recent studies applying genetically sensitive designs cast some doubt on the causality of the relationship between prenatal maternal substance use and infant and child behavioral outcomes. In this review, recent findings in this field of research are provided, with attention to correlated risk factors of maternal substance use during pregnancy and preclinical studies focusing on plausible biological pathways. Next, evidence-based interventions targeting maternal substance use during pregnancy are discussed. Finally, possible interventions targeting the correlated risk factors and recommendations for clinical work are presented.