RFamide-related peptides (RFRPs) have been heavily implicated in the control of reproductive function subsequent to their discovery more than 16 years ago. However, recent studies using genetic and pharmacological tools have challenged their importance in regulating the hypothalamic-pituitary-gonadal axis. It is generally accepted that RFRPs act as part of a wider RFamide system, which involves two receptors, called the neuropeptide FF receptors (NPFFR1 and R2), and includes the closely-related neuropeptide NPFF. NPFF has been studied ever since the 1980s and many of the functions of NPFF are also shared by RFRPs. The current review questions whether these functions of NPFF are indeed specific to just NPFF alone and presents evidence from both neuroendocrine and pharmacological perspectives. Furthermore, recently emerging new functions of RFRPs are discussed with the overall goal of clarifying the functions of RFRPs beyond the hypothalamic-pituitary-gonadal axis.