Disturbed alveolar fibrin turnover is intrinsic to acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pneumonia and is important to its pathogenesis. Recent studies also suggest disturbed alveolar fibrin turnover to be a feature of ventilator-induced lung injury (VILI). The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors, and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. Administration of anticoagulant agents (including activated protein C, antithrombin, tissue factor-factor VIIa pathway inhibitors, and heparin) and profibrinolytic agents (including plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ALI/ARDS and pneumonia. In this article, we review the involvement of coagulation and fibrinolysis in the pathogenesis of ALI/ARDS pneumonia and VILI and the potential of anticoagulant and profibrinolytic strategies to reverse pulmonary coagulopathy and pulmonary inflammatory responses.