Kisspeptin binding to its G-protein-coupled receptor KISS1R (also known as GPR54), which is expressed by gonadotropin-releasing hormone (GnRH) neurons, stimulates GnRH release and activation of the mammalian reproductive axis. Kisspeptin neurons make close contact with GnRH neurons acting at both the cell body and the nerve terminals. Kisspeptin can act directly on GnRH neurons and/or indirectly via synaptic input from other neurons to inhibit inwardly rectifying potassium channels and activate non-specific cation channels, with the effect of long-lasting depolarization and increased action potential firing rate. This review covers the recent advances in the molecular consequences of kisspeptin action on GnRH neurons and how these neuronal circuits are integrated in different species. These studies provide insight into the mechanism by which kisspeptin regulates the reproductive axis.