The close link between energy reserves, metabolic status and fertility is based on a complex network of regulatory signals, of peripheral and central origin, that participate in the joint control of energy homeostasis and reproduction, but whose nature remains to be fully elucidated. Recent experimental data suggest that the gut hormone ghrelin, regarded as signal of energy insufficiency, may operate also as pleiotropic modulator of the reproductive axis as (i) ghrelin is able to inhibit luteinizing hormone secretion in rodents and other mammals; (ii) ghrelin is a negative modifier of puberty onset in (male) rats; (iii) ghrelin and its canonical receptor are expressed in the gonads; and (iv) ghrelin conducts direct gonadal actions; testicular effects of ghrelin include inhibition of testosterone secretion, Leydig cell proliferation and expression of relevant Sertoli cell genes. In addition, evidence is also mounting that kisspeptins, encoded by the KiSS-1 gene and potent stimulators of the reproductive axis, play a crucial role for integrating energy status and fertility. Thus, expression of KiSS-1 gene at the hypothalamus is sensitive to nutritional status, and its diminished expression in situations of negative energy balance likely contributes to the suppression of reproductive function in such conditions. Moreover, leptin has been recently demonstrated to stimulate hypothalamic KiSS-1 gene expression, in different models of disturbed metabolism and hypoleptinaemia. These observations, together with the demonstration of leptin receptors in discernible KiSS-1 neurons at the hypothalamus, provide the basis for a leptin-kisspeptin pathway in the metabolic control of the reproductive axis. It is proposed that, in addition to 'classical' metabolic regulators (i.e. leptin and insulin), the gut hormone, ghrelin, and the hypothalamic neuropeptide, kisspeptin, are 'novel' players in the neuroendocrine networks that integrate energy balance and reproduction.