Platelets are the chief effector cells in hemostasis and have additional major functions in inflammation, vascular integrity, and tissue repair. Platelets and the lungs have interrelated activities. Previous studies provide evidence that platelets contribute to pulmonary vascular barrier function and are required for defense against pulmonary hemorrhage, and that the lungs can influence platelet number and distribution. There is also evidence that platelets contribute to pathologic syndromes of pulmonary inflammation and thrombosis. Thus, platelets have an ‘‘amicus or adversary’’ relationship with the lung. Recent observations and discoveries have established new paradigms relevant to influences of platelets on lung cell andmolecular biology. These new findings are in a variety of areas including thrombopoieis, nontraditional activities of platelets, new synthetic capabilities and mechanisms of post-translational gene expression, interactions of platelets with endothelial cells and contributions to alveolar capillary barrier permeability, interactions of platelets with myeloid leukocytes, and platelet involvement in stem cell signaling and vascular repair. These issues are considered in a translational approach, with an emphasis on acute lung injury and the acute respiratory distress syndrome.