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The mechanisms of epithelial injury in acute lung injury/acute respiratory distress syndrome have been of interest since the syndrome was first described. Cell therapies to replace injured epithelium are a futuristic dream; however, there is ongoing research to achieve this goal. We review research regarding the function of the epithelium in acute lung injury/acute respiratory distress syndrome, including potential novel therapies.Altered fluid clearance from the injured lungs in acute lung injury/acute respiratory distress syndrome patients has been consistently found and is an important prognostic finding. New research suggests that neutrophils that enter the lung late and which are enticed into the lung through a specific chemokine system may be important for causing lung injury. If this is the case, then blockers of this system could be a possible therapy. The role of fibrinolysis and coagulation abnormalities in lung injury due to infection and other perturbations is examined. These abnormal findings may be useful diagnostic tools for prognostication as well as targets for future therapies.Epithelial damage is a hallmark of acute lung injury/acute respiratory distress syndrome. An increased understanding of the function of these cells and of the abnormalities that occur when these lung cells are injured should allow the development of novel therapies and, perhaps, lead to replacement therapies.