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Until 2000 it was believed that gonadotropin-releasing hormone (GnRH) was the sole regulator of hypophyseal gonadotropes. In 2000, the discovery of a gonadotropin inhibitory hormone (GnIH) initiated a revolution in the field of reproductive physiology. Identification of GnIH homologues in mammals, the arginine-phenylalanine-amide (RFamide)-related peptides (RFRPs), indicated a similar function. Subsequently, further works conducted in various laboratories worldwide have shown that these neuropeptides inhibit the hypothalamic-hypophyseal axis. This review discusses the role of RFRPs in mammalian reproductive processes.