Acute respiratory distress syndrome (ARDS) is a clinically heterogenous syndrome, rather than a distinct disease.

This heterogeneity at least partially explains the difficulty in studying treatments for these patients and contributes to the numerous trials of therapies for the syndrome that have not shown benefit.

Recent studies have identified different subphenotypes within the heterogenous patient population.

These different subphenotypes likely have variable clinical responses to specific therapies, a concept known as heterogeneity of treatment effect (HTE).

Recognizing different subphenotypes and HTE has important implications for the clinical management of patients with ARDS.

In this review, we will present studies that have identified different subphenotypes and discuss how they can modify the effects of therapies evaluated in trials that are commonly considered to have demonstrated no overall benefit in patients with ARDS.

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