This review concentrates on the characteristics and functionality of endocrine neurons in the hypothalamo-neurohypophysial system, coexpressing two peptides, vasopressin and apelin. Vasopressin is synthesized in the soma of magnocellular neurons, then packaged in granules with its respective receptors. In these neurons, apelin is generated from a larger precursor proapelin and is detected in vesicles, some of them colocalize with vasopressin, for others there is a marked segregation of apelin and vasopressin immunoreactivity along the hypothalamo-hypophyseal axons. Furthermore, apelin receptors, like V1a-type and V1b-type vasopressin receptors, are synthesized by magnocellular vasopressin neurons. In lactating rodents, apelin given intracerebroventricularly inhibited the phasic electrical activity of vasopressin neurons, reduced plasma vasopressin levels and increased aqueous diuresis, showing that apelin acts as a potent diuretic neuropeptide, counteracting vasopressin actions through inhibition of vasopressin neuron activity and vasopressin release. Moreover, in response to potent physiological stimuli known to evoke increased phasic activity of vasopressin neurons (hyper-osmolarity like during dehydration), both the soma dendrites and neurohypophysial terminals loose their dense staining quality, and vasopressin is released by (i) dendrites in the extracellular space to optimize the characteristic phasic activity necessary to a sustained release of vasopressin and (ii) by terminals in blood circulation where vasopressin then ensures its main endocrine actions at kidney level (antidiuretic effect). Conversely, apelin accumulates in these neurons rather than being released into the bloodstream and probably into the nuclei. Thus, decreases in the local supply of apelin to magnocellular vasopressin cell bodies may facilitate the expression by vasopressin neurons of an optimized phasic activity, by decreasing the inhibitory actions of apelin on these neurons. Antagonistic regulation of apelin and vasopressin has a biological purpose, making it possible to maintain the water balance of the organism by preventing additional water loss via kidneys. This reveals a new physiological concept of dual and opposite functional potentiality for endocrine neurons coexpressing different neuropeptides in separate vesicles: depending on the degree of their electrical activation/inhibition, neurons release selectively the very coexpressed peptides that will ensure its accurate endocrine functions in perfect accordance with the hormonal demand.