Neuromuscular blocking agents (NMBAs) and prone position (PP) are two major adjunctive therapies that can improve outcome in moderate-to-severe acute respiratory distress syndrome. NMBA should be used once lung-protective mechanical ventilation has been set, for 48 hours or less and as a continuous intravenous infusion. PP should be used as early as possible for long sessions; in COVID-19 its use has exploded. In nonintubated patients, PP might reduce the rate of intubation but not mortality. The goal of this article is to perform a narrative review on the pathophysiological rationale, the clinical effects, and the clinical use and recommendations of both NMBA and PP.