The time around birth is accompanied by behavioural and physiological adaptations of the maternal brain, which ensure reproductive functions, maternal care and the survival of the offspring. In addition, profound neuroendocrine and neurobiological adaptations have been described with respect to behavioural and neuroendocrine stress responsiveness in rodents and human mothers. Thus, the hormonal response of the hypothalamo-pituitary-adrenal (HPA) axis and the response of the sympathetic nervous system to emotional and physical stressors are severely attenuated. Moreover, anxiety-related behaviour and emotional responsiveness to stressful stimuli is reduced with the result of general calmness. These complex adaptations of the maternal brain are likely to be a consequence of an increased activity of brain systems with inhibitory effects on the HPA axis like the oxytocin and prolactin systems, and of a reduced activity of excitatory pathways (noradrenaline, CRF, opioids). Experimental manipulation of these systems using complementary approaches indeed demonstrates their importance in these maternal brain adaptations. Maternal stress adaptations are not only important for the healthy prenatal development of the offspring by preventing excessive glucocorticoid responses and in the promotion of postnatal maternal behaviour, but are also vital for the well-being of the mother and her mental health.