Cough is the natural defense mechanism for protection of the respiratory tract. It is used to mobilize and remove secretions from the respiratory tree, moving them from the peripheral to the central airways. Effective airway clearance for individuals with cystic fibrosis is an essential component of daily therapy because of the thick and tenacious secretions that accumulate in their airways. Regardless of the airway clearance method used, effective coughing is the key part of the process. Understanding airway physiology and utilizing the equal pressure point and the collateral ventilation system between airways will make airway clearance activities most effective. Finding a match between an effective airway clearance method that uses cough effectively and a patient's preference is the challenge for the care provider.