© 2016 the American Physiological Society. The major role of red blood cells (RBCs) is to deliver oxygen and remove carbon dioxide within organisms through the unique properties of hemoglobin. Although beneficial within RBCs, when outside hemoglobin and its breakdown products (heme, iron) induce proinflammatory responses affecting various cellular responses. Although these effects are considered to be prominent in disorders with increased hemolysis, recent evidence uggests that this process may be active in nonhemolytic disorders such as acute lung injury/acute respiratory distress syndrome. This perspectives article focuses on data related to red cell products in nonhemolytic disorders and the potential to target these factors in acute lung injury/acute respiratory distress syndrome.