Reproductive success and ultimately species survival at a population level is contingent on a plethora of neuroendocrine signals working in concert to regulate gonadal function and reproductive behavior. Among these, the neuropeptide kisspeptin (encoded by the KISS1/Kiss1 gene) has emerged as the master regulator of the hypothalamic-pituitary-gonadal axis. Besides the hypothalamus, both kisspeptin and its cognate receptor are extensively expressed throughout cortico-limbic brain structures in rodents and humans, which are regions traditionally implicated in behavioral and emotional responses. Thus, there exists a neuroanatomical framework through which kisspeptin can integrate reproductive behavior and emotional regulation with the reproductive axis. Accordingly, this sets the scene for recent findings derived from an assortment of species, including humans, unveiling kisspeptin as an important gatekeeper of reproductive behavior and emotional control. Herein, we summarize the major preclinical animal and human experimental evidence identifying kisspeptin as a key neuromodulator of reproductive behavior and emotional state. Such findings have laid the foundations for clinical applications of kisspeptin-based therapies for patients with related reproductive and psychosexual disorders.