Acute respiratory distress syndrome (ARDS) is a collection of clinical syndromes characterized by a variety of heterogeneous causes. It includes diffuse lung diseases of various etiologies that ultimately lead to refractory hypoxia and severe acute respiratory failure. Despite advances in research and treatment of ARDS, its incidence and mortality continue to pose significant challenges in clinical practice. Since its inception in 1967, the definition of ARDS has undergone several revisions that have generated controversy and influenced the implementation of diagnostic and treatment strategies. At present, ARDS remains a formidable obstacle to both diagnosis and treatment. This article undertakes a comprehensive review of the evolution of ARDS definitions, examines the current diagnostic paradigm, and explores its far-reaching consequences. Our aim is to identify research directions, both in the realm of basic science and clinical practice, that are consistent with the nature of this complex disorder.