Kisspeptins, the products of the KISS1 gene, are a family of structurally related peptides with ability to activate the G protein-coupled receptor 54 (GPR54 or KISS1R). Kisspeptins were first reported to operate as metastasis suppressor factors. Yet, in late 2003, the indispensable role of the so-called KISS1/GPR54 system in the control of reproduction was disclosed by the demonstration of the state of impuberism and hypogonadotropic hypogonadism in humans and mice bearing inactivating mutations of KISS1R. Since then, an ever growing number of molecular and physiological studies have helped to characterize the essential functions of kisspeptins and their receptor in the control of key aspects of reproductive maturation and function. We will review in this presentation the experimental data, obtained mostly in laboratory rodents, that have defined (i) the involvement and mechanism of action of kisspeptins and KISS1R in the control of puberty onset; (ii) the roles of specific populations of kisspeptin-producing neurons at the hypothalamus in mediating the feedback effects of sex steroids; (iii) the function of kisspeptins in the generation of the pre-ovulatory surge of gonadotropins; and (iv) the contribution of KiSS1 neurons to the metabolic regulation of fertility. Altogether, the above data illustrate the paramount importance of kisspeptins and KISS1R in the neuroendocrine networks governing reproductive function, where kisspeptin neurons are ideally placed to operate as an essential integrative 'node' driving the secretion of hypothalamic GnRH and, thereby, fertility.