Summary Individual variation in opioid sensitivity can have a profound impact on the safety and efficacy of equine veterinary treatments, with the ability to adequately manage equine pain in a clinical setting currently limited. This review aims to explore the overlap between biological mechanisms associated with opioid metabolism and those mechanisms associated with coat colour in horses as has been documented in humans, with particular focus on the melanocortin‐1 receptor (MC1R) gene. In the future, the use of the MC1R coat colour genotype could help to indicate variable opioid sensitivities thereby greatly improving the use of opioids in clinical settings. The MC1R gene has a well‐established role in melanogenesis and pigment switching, but involvement in the pain‐modulating periaqueductal grey (PAG) descending pathway and in immune responses, both of which contain opioid receptors, has also been suggested in humans. However, this relationship between opioid metabolism and the connection to the three known MC1R variants (EE, Ee and Eea) in horses is yet to be explored.