Addiction remains a significant public health concern. Despite numerous public health initiatives, many parents continue to use substances during the prenatal and postpartum period. While stress has been implicated in the maintenance of substance use disorders more generally, we propose that parenting stress specifically increases vulnerability to substance use in adults caring for young children. To explore this notion, we first consider the neurobiology of the adult transition to parenthood and the value of adopting a parenting-specific approach to understanding addictive processes. Next, we consider the neurobiology of addiction and parenting before directly addressing parenting stress in the context of addiction. Finally, we describe current interventions with parents that incorporate the management of negative affect to enhance caregiving quality and decrease substance use. Taken together, this article proposes that the unique demands of caring for a developing child may be more stressful above and beyond other forms of stress. As a consequence, intervention approaches that target stress in the parenting role hold promise for decreasing parental substance abuse.