Background Klippel-Feil syndrome (KFS) is a rare congenital disease characterized by fused cervical vertebrae, and often associated with other anomalies of other organs. The patients with KFS are at a increased risk for difficult airway. Objective We intend to discuss the challenging anesthetic management in KFS. Content This review summarizes the clinical manifest and diagnosis and anesthetic management, focusing on the airway management in KFS. Trend A comprehensive preoperative assessment on cervical anomalies and airway examination can contribute to make a more rational method of airway and anesthetic management in KFS, avoiding neurological injury and promoting the perioperative safety of patients with KFS.