The acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are part of a devastating syndrome characterized by acute onset, hypoxemia, and bilateral infiltrates on chest X-rays. ALI/ARDS arises from the lungs response to local or systemic aggression in which local inflammation and coagulation disorders lead to increased inflammatory pulmonary edema. ARDS is a major cause of morbidity, death, and cost in intensive care units. ALI and ARDS are associated with increased procoagulant and reduced fibrinolytic activities mainly in alveoli and interstitial spaces. Fibrin deposition, which is the hallmark of early phase ALI, stimulates fibroblast aggregation and collagen secretion, contributing to pulmonary fibrosis. The only clinical intervention that has a significant impact on mortality in ARDS is the use of low tidal volume ventilation. ARDS has many coagulation disorders in common with severe sepsis, where recombinant human activated protein C has reduced mortality, hastened improvement in respiratory dysfunction, and shortened the duration of mechanical ventilation. Future clinical trials in ALI/ARDS should evaluate the potential benefits of anticoagulants administered systemically or locally in the lungs.