Naltrexone, an opioid antagonist, traditionally used in addiction treatment has demonstrated promising therapeutic potential in dermatology. Understanding its dual dosing paradigms and mechanisms of action therefore becomes crucial for expanding its dermatological applications. Clinical evidence supports naltrexone’s efficacy in Hailey-Hailey disease, lichen planopilaris, psoriasis, atopic dermatitis, hidradenitis suppurativa, chronic urticaria, and prurigo nodularis. Low-dose naltrexone (LDN) demonstrates distinct immunomodulatory and anti-inflammatory effects with a favourable safety profile, while high-dose naltrexone (HDN) shows utility primarily in pruritic conditions but with more frequent mild adverse effects. However, all applications still remain off-label. Further research through randomized controlled trials therefore becomes essential to validate the efficacy of naltrexone for the same. Future studies focusing on the development of topical naltrexone formulations and combination therapy protocols may serve in expanding the utility of naltrexone for various dermatoses.