The acute respiratory distress syndrome (ARDS) is a severe condition causing approximately 40% mortality in about 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. Common clinical disorders associated with ARDS include sepsis, pneumonia, aspiration of gastric contents, and major trauma. The lung injury is primarily caused by neutrophil- and platelet-dependent damage to the endothelial and epithelial barriers of the lungs. Resolution is delayed due to injury to the lung epithelial barrier, which prevents the removal of alveolar edema fluid and depletes surfactant. Lymphocytes may play a role in resolving lung injury. Lung-protective ventilatory strategies have significantly reduced mortality, but there is no effective pharmacological therapy. Cell-based therapies and other novel treatments under clinical trial may provide new options for ARDS management.The acute respiratory distress syndrome (ARDS) is a severe condition causing approximately 40% mortality in about 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. Common clinical disorders associated with ARDS include sepsis, pneumonia, aspiration of gastric contents, and major trauma. The lung injury is primarily caused by neutrophil- and platelet-dependent damage to the endothelial and epithelial barriers of the lungs. Resolution is delayed due to injury to the lung epithelial barrier, which prevents the removal of alveolar edema fluid and depletes surfactant. Lymphocytes may play a role in resolving lung injury. Lung-protective ventilatory strategies have significantly reduced mortality, but there is no effective pharmacological therapy. Cell-based therapies and other novel treatments under clinical trial may provide new options for ARDS management.