Women's mental health during pregnancy has important implications not only for the well-being of the mother, but also for the development, health, and well-being of her unborn child. A growing body of empirical evidence from population-based studies suggests that two indicators of women's mental health during pregnancy—psychosocial stress and social support—may exert a significant influence on fetal development and infant birth outcomes, such as birth weight and length of gestation, even after controlling for the effects of established sociodemographic, obstetric, and behavioral risk factors. This paper describes the role of three major biological systems involved in the physiology of pregnancy and stress physiology: neuroendocrine, immune/inflammatory, and cardiovascular systems. These systems have been hypothesized to mediate the effects of maternal mental health on fetal developmental and health outcomes, and a central role has been proposed for placental corticotropin-releasing hormone in this process. However, not all women reporting high prenatal stress and/or low social support proceed to develop adverse birth outcomes, raising the question of the determinants of susceptibility/vulnerability in the context of high stress and/or low social support. In this context, the role of race/ethnicity and genetic predisposition are. discussed as two promising avenues of further investigation.