Cystic fibrosis (CF) is a complex autosomal recessive multisystem disorder characterized by defective chloride ion transport, resulting in thick mucus secretions primarily affecting the respiratory, gastrointestinal, and reproductive systems but also with frequent otorhinolaryngological (ENT) involvement, often underrecognized in clinical practice. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Otorhinolaryngological (ENT) involvement significantly contributes to morbidity among CF patients, commonly presenting with chronic rhinosinusitis, nasal polyposis, and conductive hearing impairment. This review explores ENT manifestations associated with CF in detail, examining pathophysiological mechanisms, current diagnostic methods, and contemporary therapeutic strategies, including emerging treatmentsand collaborative interdisciplinary management. This manuscript presents a structured ENT clinical algorithm based on the CFTR acronym—Conductive hearing, Functional nose, Throat, and Respiratory integration—to guide systematic assessment and interdisciplinary management. Drawing from contemporary literature and clinical experience, the CFTR ENT algorithm provides a practical framework for early detection, evaluation, and referral, with pediatric and adult-specific considerations. It aims to support ENT specialists, pulmonologists, and CF care teams in improving patient outcomes through integrated, symptom-specific intervention.