Body energy balance and metabolic signals are important modulators of puberty and reproductive function, so that perturbations of metabolism and energy reserves (ranging from persistent energy insufficiency to morbid obesity) are frequently linked to reproductive disorders. The mechanisms for the tight association between body metabolic state and reproduction are multifaceted, and likely involve numerous peripheral hormones and central transmitters. In recent years, a prominent role of kisspeptins in the central pathways responsible for conveying metabolic information into the brain centers responsible for reproductive control, and specifically GnRH neurons, has been proposed on the basis of a wealth of expression and functional data. In this chapter, we will summarize such evidence, with special attention to the potential (direct and/or indirect) interaction of leptin and kisspeptin pathways. In addition, other potential metabolic modulators of kisspeptin signaling, as well as some of the putative molecular mechanisms for the metabolic regulation of Kiss1 will be briefly reviewed. Conflictive data, including those questioning an essential role of Kiss1 neurons in mediating leptin effects on the reproductive axis, will be also discussed. All in all, we aim to provide an integral and balanced view of the physiological relevance and potential mechanisms for the metabolic control of the kisspeptin system, as important pathway for the integral regulation of energy balance, puberty onset, and fertility.