High-frequency oscillation (HFO), applied to either the airway or chest wall, has been associated with changes in sputum attributes and clearance. The evolution of evidence, both in vitro and in vivo, supporting the use of HFO is reviewed. Devices that apply HFO to the airway range from the relatively simple mechanical Flutter and Acapella devices to the more complex Percussionaire Intrapercussive Ventilators. and the Hayek Oscillator are designed to provide high-frequency chest wall compression. Operation and use of these devices are described with examples of differentiation of device types by characterization of flows, and airway and esophageal pressures. Although HFO devices span a broad range of costs, they provide a reasonable therapeutic option to support secretion clearance for patients with cystic fibrosis.