Tissue response to insults is similar regardless of the tissue involved, and occurs in two sequential and interconnected steps, inflammation and fibroproliferation. Adult respiratory distress syndrome (ARDS) is a disease characterized by acute onset of diffuse and severe inflammatory reaction of the lung parenchyma with loss of compartmentalization, resulting in protein rich exudative edema. Following tissue injury, a complex pattern of responses begins to repair the lung. Ineffective repair is evident histologically with extensive pulmonary fibroproliferation and clinically with fever (without a source of infection) and inability to improve lung function. We will review recent observations indicating that an exaggerated pulmonary inflammatory response plays a key role in the progression of ARDS. We will provide a unifying pathogenetic model of ARDS, showing how the evolution from acute to chronic inflammation explains the progression of histological, laboratory, clinical, and physiological findings seen during the course of unresolving ARDS.