Melanocortins are the products of the precursor protein proopiomelanocortin (POMC) with extensive localization in the central nervous system and peripheral tissues. Melanocortins play important roles in the skin, stress response, immune system, feeding behavior, and sexual function. In recent years, the -melanocyte stimulating hormone (-MSH) and melanocortin-4 receptor (MC4R) have received considerable attention for their regulation of energy homeostasis and reproduction. Previous studies have shown that POMC, -MSH, and MC4R regulate food intake and the reproductive system by mediating the secretion of hormones related to the hypothalamic-pituitary-gonadal (HPG) axis. In this review, we summarize the physiological functions of POMC, -MSH, and MC4R in energy homeostasis and reproduction. We also summarize the results of several studies reporting the pharmacological characteristics of teleost MC4R and discuss the potential commercial applications in aquaculture.