Background: Cystic fibrosis (CF) is the most common severe autosomal recessive disorder in Caucasians. Viscous secretionstypically obstruct the lungs, pancreas, and gastrointestinal tract. As disease management improves, patients will increasingly seek care for conditions such as acne. Isotretinoin therapy for acne in patients with CF is controversial owing to concerns that the medication may exacerbate CF-related hepatic, pulmonary, and ocular complications.Purpose: We describe two patients with CF treated with isotretinoin from our clinic and also provide a literature review of 11 similar cases. We describe patient outcomes, common complications, and the risks for severe adverse effects.Materials and methods: The clinical courses of two patients with CF who were treated with isotretinoin for moderate-severe acne are presented. Using PubMed, we analyzed previous case reports of patients with CF who were prescribed isotretinoin and review complications associated with systemic retinoids.Results: Based on a synthesis of the literature and our own experience, it appears that isotretinoin therapy for CF patients with moderate-severe acne may be an appropriate option when clinically indi ated. If dermatologists monitor lab values and adverseeffects carefully, patients with CF can benefit from isotretinoin therapy.