The onset of labour is characterised by dramatic changes in uterine tissue responsiveness to external hormonal stimuli. These signals, many arising from the placenta, target the myometrial smooth muscle to facilitate inhibition of quiescent pathways and activation of pro-contractile mechanisms. An important signal appears to be corticotropin-releasing hormone (CRH), the hypothalamic peptide that controls mammalian survival and response to stressful stimuli. CRH is secreted by human placenta during pregnancy; however, its role during pregnancy and labour is still an enigma. CRH plasma levels of rise exponentially as pregnancy progresses towards term and might be an important predictor of the duration of human gestation. Furthermore, there are substantially increased concentrations of maternal circulating CRH in abnormal pregnancy states; in some women with idiopathic preterm labour, concentrations of CRH increase up to 10 weeks before the development of any symptoms. Placental CRH targets multiple feto-maternal tissues, including the myometrium, placenta and fetal adrenals. These tissues express a wide network of specific G-protein coupled receptors. Current evidence suggests that activation of CRH-Rs is involved in the mechanisms regulating uterine transition from relaxation to active contractions, in placental vascular tone, and modulation of fetal adrenal function. These receptors have various functional properties, depending on the receptor subtype, the ability of agonists to activate specific signalling cascades and the stage of pregnancy. In addition, their function is dependant upon other intracellular signals via communication between signalling cascades, suggesting potential multiple roles of CRH and other CRH-like peptides during pregnancy and labour.