Progesterone and allopregnanolone have crucial and different roles in brain development, function and recovery after injury. Pregnancy is characterized by an increased synthesis of progesterone and its neuro-active metabolites by the placenta, maternal and fetal brain. This supports the critical role of these steroids in maternal brain adaptation during pregnancy and development of the fetal brain. Moreover, allopregnanolone may play a brain-protective role during complications of pregnancy, complications of pregnancy, such as preterm delivery or intrauterine growth restriction (IUGR), by reducing the impact of hypoxia and excitotoxic brain damage or impairment myelination. Behavioral consequences of altered progesterone/allopregnanolone fetal brain programming have also been hypothesized, although further evidence is needed. New potential applications of allopregnanolone as a treatment strategy have also been proposed, addressing unmet clinical needs in perinatal care.