The hypothalamo-neurohypophysial system is comprised of magnocellular neurones that synthesise the neuropeptides oxytocin or vasopressin. As neurohormones, these peptides intervene in the regulation of vital functions such as parturition, lactation, osmotic and cardiovascular regulation. The release of these peptides in the general circulation depends on the electrical activity of their parent neurones, which in turn is regulated by the activity of their afferent inputs conveying distinct information. Thus, in view of the diversity of information governing the activity of magnocellular neurones, it is crucial that the system adapts the appropriate release of oxytocin and vasopressin upon physiological demand. Until recently, it was considered that only neurones could provide such adaptation and regulation. However, a third partner of the synapse, the astrocyte, has been shown to provide further control. Astrocytic processes are in proximity of the magnocellular neurones and their synapses, well positioned to detect and modulate synaptic signals. For instance, astrocytes detect a synaptic signal owing to their diverse neurotransmitter/neuropeptide receptors. In addition, they release a variety of neuroactive substances (i.e. gliotransmitters), which in turn modulate synaptic activity. An important gliotransmitter is the amino acid, d-serine, which, together with glutamate, activates NMDA receptors. Once activated, NMDA receptors govern the weight of individual inputs on magnocellular neurones and thus the impact of distinct types of information on neuronal activity. As reviewed here, numerous observations show that astrocytes must be considered as key elements in the functioning of the hypothalamo-neurohypophysial system.