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Many infants continue to require invasive ventilation, despite major advances in perinatal care including widespread use of antenatal steroid therapy, exogenous surfactant therapy and non-invasive respiratory support. Ventilation induced lung injury (VILI) is a complication of invasive ventilatory support that prolongs duration of supportive care. Ventilation induced lung injury in the developing lung has lifelong implications for respiratory well-being due to failure of alveolarisation and abnormal airspace development. The proportion of infants requiring mechanical ventilation increases at lower gestations: extremely preterm infants are additionally extremely vulnerable to injury. Consequently, ventilation research and device development over the past two to three decades has focused intensely on new therapies that facilitate life support with minimal risk of iatrogenic injury. Both extracorporeal membrane oxygenation (ECMO) and high-frequency ventilation offer opportunities for lung protective ventilation whilst minimising rheotrauma resulting from either excessive cyclic volume oscillations or repeated re-inflation of atelectatic air spaces. High-frequency oscillation is a unique and the most well-known and used form of high-frequency ventilation. HFOV arose initially from observations by Henderson of patterns of smoke blown down a tube, and was subsequently described in more detail by Lunkenheimer in the early seventies (4, 28). HFOV has now emerged into a comprehensive ventilatory strategy applied throughout the world as both an a priori and rescue ventilatory modality. 3.2 Definition Distinguishing characteristics of contemporary HFOV include: 1. a frequency range from 3-20 Hz (180 to 1200 breaths/minute); 2. active inspiratory and expiratory phases; 3. tidal volumes approximating anatomical dead space volume. 3.3 Devices and mechanisms for generating active expiratory flow A range of technical principles are used to produce oscillatory ventilatory waveforms in different devices. The oscillations divert small volumes of gas to the patient at high frequency: the mechanically driven oscillations resulting in active inspiration and active expiration. Mean airway pressure is created through the pressure drop of the bias flow in combination with an expiratory resistance. True oscillators achieve roughly matching magnitude of the negative and positive pressure deflections when equal inspiratory and expiratory cycle durations are used. Matched negative and positive pressure deflections can be achieved via several different mechanisms including a linear motor piston pump, an electromagnetically driven vibrating diaphragm (loudspeaker) or via a combination of servo controlled inspiratory valve and an expiratory venturi jet (which is generating sub-atmospheric pressures). Examples of contemporary oscillators include the Sensormedics SM3100A, SM3100B, Humming V, the Flowline Dragonfly, the Heinen and Löwenstein Leoni Plus, the Acutronics Fabian, the Stephan SHF3000, the SLE5000 and the Dräger Babylog 8000plus and Babylog VN500. Although oscillators are traditionally classified according to the oscillatory flow generating mechanism, the function, capabilities and limitations of each device are of greater clinical relevance to practical application and potential physiological efficacy. A key differentiation is the frequency composition of the oscillatory waveform: oscillators generating sine waves with relatively “pure” fundamental frequency content contrast with those producing more complex and often square waveforms comprising multiple frequencies (1, 2). Although more complex waveforms may enhance gas mixing and regional ventilation homogeneity, the effect of the potential shear effects arising from more turbulent and inertive2 oscillatory flow on airway wall properties is