BACKGROUND Morbihan disease (MD) is characterized by persistent erythema and solid edema of the upper two-thirds of the face. It is generally regarded as a late-stage complication of rosacea, although its etiology is poorly understood. The standard therapeutic management includes systemic anti-inflammatory medications; however, the clinical response, if any, is often unsatisfactory. We review the current challenges and a promising new option for the treatment of MD. OBSERVATIONS Five cases of MD were treated with long-term (>6 months; mean, 16 months) oral isotretinoin, with documented nonrecurrence. The mean sustained daily dose was 60 mg/d (range, 40-80 mg/d), and the mean cumulative dose was approximately 285 mg/kg (range, 170-491 mg/kg). The total treatment period ranged from 10 to 24 months, with a mean disease-free follow-up period of 9 months (range, 1-24 months). A substantial clinical improvement was not noted until 6 months of treatment in all 5 cases. CONCLUSIONS We report 5 cases of MD that were successfully treated with long-term oral isotretinoin, with lasting results. Further research is required to better understand the pathogenesis of MD and isotretinoin's mechanism of action in this condition.