Adrenocorticotropic hormone (ACTH) and α-melanocyte stimulating hormone (α-MSH) are centrally acting melanocortin peptides with numerous reported functions, including induction of excessive grooming and antipyresis, among others. Also reported is a role for melanocortins in aspects of opiate action. Although early work examined the effects of ACTH and MSH on opiate-induced behaviors, further progress has been limited. Recently, however, advances in the identification and characterization of melanocortin receptor (MC-R) subtypes have provided novel tools with which to study interactions between melanocortins and addiction. The present review discusses the effects of ACTH and MSH on opiate-induced behaviors and relates these findings to more recent reports on the regulation of melanocortin systems by exogenous opiates. Emerging from these data is the possibility that melanocortin receptor activation, specifically at the MC4-R subtype, may act to antagonize certain properties of exogenous opiates, including perhaps addiction.