To maximise reproductive success, organisms restrict breeding to optimal times of the day or year, when internal physiology and external environmental conditions are suitable for the survival of both parent and offspring. To appropriately coordinate reproductive activity, internal and external standing is communicated to the hypothalamic-pituitary-gonadal axis via a coordinated balance of stimulatory and inhibitory neurochemical systems. The cumulative balance of these mediators ultimately drives the pattern of gonadotrophin-releasing hormone secretion, a neurohormone that stimulates pituitary gonadotrophin secretion. Until 2000, a complementary inhibitor of pituitary gonadotrophin secretion had not been identified. At this time, a novel, avian hypothalamic peptide capable of inhibiting gonadotrophin secretion in cultured quail pituitary cells was uncovered and named gonadotrophin-inhibitory hormone (GnIH). Subsequently, the presence and functional role for the mammalian orthologue of GnIH, RFamide-related peptide, (RFRP-3), was examined, confirming a conserved role for this peptide across several rodent species. To date, a similar distribution and functional role for RFRP-3 have been observed across all mammals investigated, including humans. This overview summarises the role that RFRP-3 plays in mammals and considers the implications and opportunities for further study with respect to reproductive physiology and the neural control of sexual behaviour and motivation.