This review describes the management of mechanical ventilation in patients with acute respiratory distress syndrome, including in those with coronavirus disease 2019. Low tidal volume ventilation with a moderate to high positive end-expiratory pressure remains the foundation of an evidence-based approach. We consider strategies for setting positive end-expiratory pressure levels, the use of recruitment maneuvers, and the potential role of driving pressure. Rescue therapies including prone positioning and extracorporeal membrane oxygenation are also discussed.