Stress and adverse environmental surroundings result in suboptimal conditions in a pregnant mother such that she may experience poor pregnancy outcome including complete pregnancy failure and preterm labor. Furthermore her developing baby is at risk of adverse programming, which confers susceptibility to long term ill health. While some mechanisms at the feto-maternal interface underlying these conditions are understood, the underlying cause for their adverse adaptation is often not clear. Progesterone plays a key role at many levels, including control of neuroendocrine responses to stress, procuring the required immune balance and controlling placental and decidual function, and lack of progesterone can explain many of the unwanted consequences of stress. How stress that is perceived by the mother inhibits progesterone secretion and action is beginning to be investigated. This overview of maternal neuroendocrine responses to stress throughout pregnancy analyses how they interact to compromise progesterone secretion and precipitate undesirable effects in mother and offspring. (C) 2010 Elsevier Inc. All rights reserved.