Hyperprolactinemia is a common endocrine syndrome in people of reproductive age and occurs in 15—20% of women with menstrual irregularities and infertility. Recent studies have shown that prolactin does not affect the reproductive system directly, but indirectly, through a network of hypothalamic KISS neurons that produce kisspeptin, a powerful activator of neurons that produce gonadotropin-releasing hormone (GnRH). It is known that prolactin directly inhibits the secretion of kisspetin and thus, leads to the termination of pulsating secretion of GnRH and, consequently, to a decrease in the level of luteinizing hormone and anovulation. In turn, kisspeptin affects dopaminergic neurons and reduces their activity, thus providing an increase in prolactin levels. Both of these regulatory mechanisms are estrogen-dependent. Studies have shown that the administration of kisspeptin to patients with pathological hyperprolactinemia leads to the restoration of pulsating secretion of GnRH, which provides ovulation. This review analyzes the latest data on the interaction of kisspeptin and prolactin, focuses on the interaction between them in experimental animal models and in humans. The field of interaction of these biologically active compounds seems to be extensive and requires further research for complete understanding of the pathogenesis of reproductive dysfunction in hyperprolactinemia.