The last decade has seen increased appreciation of ventilator-induced lung injury. The understanding that the process of mechanical ventilation can itself damage lungs has spurned the search for ventilation strategies that are more lung protective. High-frequency oscillatory ventilation is a mode of high-frequency ventilation that may accomplish all of the current goals of lung protection. Historically, much of the data evaluating high-frequency oscillatory ventilation came from neonatal and pediatric populations. In the past year, a number of provocative and exciting studies have been published that contribute significantly to our understanding of high-frequency oscillatory ventilation, its role in preventing and reducing ventilator-induced lung injury, and its use in the support of adult patients with lung injury. In this article, we discuss the current understanding of high-frequency oscillatory ventilation and highlight the most recent literature addressing its application in adult patients with acute respiratory distress syndrome.