Prolactin (PRL) is an important regulator of multiple biological functions, but a specific PRL-releasing factor, PRL-releasing peptide (PrRP), was isolated only recently from mammals and teleosts. Although this peptide seems to be a strong candidate for being a physiologically relevant stimulator of PRL expression and secretion in teleost pituitary and peripheral organs, it may not be a typical or classic hypothalamic releasing factor in rats. We now know that its biological actions are not limited solely to PRL stimulation, because it is also a neuromodulator of several hypothalamus-pituitary axes and is involved in some brain circuits with the regulation of food intake and cardiovascular functions. Moreover, it plays a direct role in hypertension and retinal information processing. It is the purpose of this review to provide a comprehensive survey of our current knowledge of PrRP and to provide a comparative point of view.