The transition to parenthood is perhaps the only time in adult life when the brain changes to such a significant degree in such a short period, particularly in birthing parents. It is also a time when there is an increased risk of developing a mental illness, which may be due, in part, to the increased neuroplasticity. Thus, we must develop interventions and treatments that support parents and promote parental brain health. This review will highlight key findings from current research on how human brain structure and function are modified with 1) the transition to parenthood, 2) parenting stress and perinatal mental illness, and 3) treatments aimed at promoting perinatal mental health. The focus will be on birthing parents and mothers, but brain changes in non-birthing parents will also be discussed. Improvements in our understanding of the parental brain, in health and with illness, will promote the well-being of generations to come.