This article discusses common ocular manifestations of cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator-related disorders (CFTR-RD). A structured approach for assessing and treating patients with CF/CFTR-RD seeking corneal refractive surgery is proposed, as well as a novel surgical risk scoring system. We also report two patients with various manifestations of CFTR dysfunction who presented for refractive surgery and the outcomes of the procedures. Surgeons seeking to perform refractive surgery on patients with CF/CFTR-RD should be aware of mild to severe clinical manifestations of CFTR dysfunction. Specific systemic and ocular manifestations of CF include chronic obstructive pulmonary disease (COPD), bronchiectasis, recurrent pulmonary infections, CF-related diabetes and liver disease, pancreatic insufficiency, conjunctival xerosis, night blindness, meibomian gland dysfunction (MGD), and blepharitis. Corneal manifestations include dry eye disease (DED), punctate keratitis (PK), filamentary keratitis (FK), xerophthalmia, and decreased endothelial cell density and central corneal thickness. Utilization of the appropriate review of systems (ROS) and screening tests will assist in determining if the patient is a suitable candidate for refractive surgery, as CF/CFTR-RD can impact the health of the cornea. Collaboration with other medical professionals who care for these patients is encouraged to ensure that their CF/CFTR-RD symptoms are best controlled via systemic and other treatment options. This will assist in reducing the severity of their ocular manifestations before and after surgery.