In this PACULit episode, the focus is on the efficacy of neuromuscular blocking agents (NMBAs) in ARDS, with emphasis on patients who have high respiratory system elastance. The discussion reviews pivotal trials (ACURASYS showing mortality benefit with early cisatracurium vs ROSE showing no clear survival advantage), explores how sedation depth and lung mechanics may influence outcomes, and highlights recent analyses suggesting elastance-defined subgroups might benefit from paralysis. Mechanistic rationale (improved patient-ventilator synchrony and reduced lung stress) is weighed against risks such as ICU-acquired weakness and delirium, along with practical considerations like train-of-four monitoring, dosing duration, and interactions with corticosteroids. The episode underscores a shift toward phenotype-guided therapy, the need for prospective trials targeting high-elastance ARDS, and emphasizes individualized risk–benefit assessment and multidisciplinary collaboration to optimize NMBA use.