Objective:Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome whose diagnosis and therapy are still in question.The aim of this review was to discuss the current challenge for the diagnosis and treatment of ARDS.Data Sources:Data sources were the published articles in English through December 2017 in PubMed using the following key words:acute respiratory distress syndrome, definition,diagnosis, therapy, lung protective strategy, right ventricular dysfunction, and molecular mechanism.Study Selection:The selection of studies focused on both preclinical studies and clinical studies of therapy of ARDS.Results:The incidence of ARDS is still high,and ARDS causes high intensive care units admissions and high mortality.The Berlin Definition proposed in 2012 is still controversial owing to lack of sensitivity and specificity.ARDS is still under recognition and it is associated with high mortality.Lung protective strategies with low tidal volume (VT) and lung recruitment should consider the physiology of ARDS because ARDS presents lung inhomogeneity;the same low VT might increase local stress and strain in some patients with low compliance,and lung recruitment could injure lungs in ARDS patients with low recruitability and hemodynamic instability.Acute cor pulmonale is common in severe ARDS.ARDS itself and some treatments could worsen acute cor pulmonale.Molecular understanding of the pathogenic contributors to ARDS has improved,but the molecular-associated treatments are still under development.Conclusions:ARDS is a devastating clinical syndrome whose incidence and mortality has remained high over the past 50 years.Its definition and treatments are still confronted with challenges,and early recognition and intervention are crucial for improving the outcomes of ARDS.More clinical studies are needed to improve early diagnosis and appropriate therapy.