The acute respiratory distress syndrome (ARDS) is a severe condition causing 40% mortality in approximately 200,000 critically ill patients annually in the United States. ARDS is characterized by protein-rich pulmonary edema leading to severe hypoxemia and impaired carbon dioxide excretion. It is associated with conditions such as sepsis, pneumonia, aspiration, and major trauma. Lung injury in ARDS is primarily due to neutrophil- and platelet-mediated damage to the endothelial and epithelial barriers of the lung. Resolution is delayed due to injury to the lung epithelial barrier, preventing the removal of alveolar edema fluid and reducing surfactant availability. Lymphocytes may play a role in resolving lung injury. Lung-protective ventilation strategies have significantly reduced mortality, but no effective pharmacologic therapy exists. Cell-based therapies and other experimental treatments are being tested. ARDS pathogenesis involves mechanisms leading to protein-rich pulmonary edema and impaired removal of edema fluid and inflammatory cells. Lung endothelial injury is a key initial factor, with increased vascular permeability causing edema. Neutrophils and platelets contribute to endothelial injury through the release of toxic mediators. Alveolar epithelial injury is also critical, with neutrophils playing a major role in increasing epithelial permeability. Ventilator-associated lung injury, particularly with high tidal volumes and pressures, exacerbates the condition. Resolution of ARDS involves clearing pulmonary edema and resolving inflammation, with mechanisms including epithelial repair and lymphocyte involvement. Current treatment focuses on supportive care, with promising new approaches including cell-based therapies and statin therapy. Despite advances, there is no proven specific treatment, but lung-protective ventilation has improved outcomes. Genetic and environmental factors influence ARDS susceptibility and severity, and further research is needed to understand these mechanisms and develop effective therapies.The acute respiratory distress syndrome (ARDS) is a severe condition causing 40% mortality in approximately 200,000 critically ill patients annually in the United States. ARDS is characterized by protein-rich pulmonary edema leading to severe hypoxemia and impaired carbon dioxide excretion. It is associated with conditions such as sepsis, pneumonia, aspiration, and major trauma. Lung injury in ARDS is primarily due to neutrophil- and platelet-mediated damage to the endothelial and epithelial barriers of the lung. Resolution is delayed due to injury to the lung epithelial barrier, preventing the removal of alveolar edema fluid and reducing surfactant availability. Lymphocytes may play a role in resolving lung injury. Lung-protective ventilation strategies have significantly reduced mortality, but no effective pharmacologic therapy exists. Cell-based therapies and other experimental treatments are being tested. ARDS pathogenesis involves mechanisms leading to protein-rich pulmonary edema and impaired removal of edema fluid and inflammatory cells. Lung endothelial injury is a key initial factor, with increased vascular permeability causing edema. Neutrophils and platelets contribute to endothelial injury through the release of toxic mediators. Alveolar epithelial injury is also critical, with neutrophils playing a major role in increasing epithelial permeability. Ventilator-associated lung injury, particularly with high tidal volumes and pressures, exacerbates the condition. Resolution of ARDS involves clearing pulmonary edema and resolving inflammation, with mechanisms including epithelial repair and lymphocyte involvement. Current treatment focuses on supportive care, with promising new approaches including cell-based therapies and statin therapy. Despite advances, there is no proven specific treatment, but lung-protective ventilation has improved outcomes. Genetic and environmental factors influence ARDS susceptibility and severity, and further research is needed to understand these mechanisms and develop effective therapies.