Acute lung injury/acute respiratory distress syndrome is a clinical syndrome that describes a single common end point: severe injury to the alveolar capillary membrane and the development of proteinaceous edema. Forty years of clinical and basic science research have elaborated many of the pathophysiologic mechanisms that link initiating insults to the development of alveolar membrane failure. A combination of genetics, comorbid conditions, inciting events, and factors yet to be discovered may uniquely alter the expression of these mechanisms in the individual patient.