Kisspeptin is the neuropeptide product of the Kiss1 gene, which is vital for the stimulation of gonadotropin-releasing hormone (GnRH) neurons. In addition to roles in puberty and fertility, kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GnRH neurons. This pathway has proven to be important for the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive) fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC) and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin will be questioned. Furthermore, in addition to being expressed in GnRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting kisspeptin may have additional functions outside of governing reproductive status. Interestingly, kisspeptin neurons located in the arcuate nucleus are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a role in energy balance and our observations indicated that Kiss1r KO mice displayed late onset obesity. Moreover, recent data suggest that this obesity may be primarily due to altered uncoupling protein-1 (UCP1) mRNA expression in brown adipose tissue. Thus, in addition to regulating reproduction, kisspeptin signaling may also be an important regulator of metabolism and body weight.