The primary focus of research into the pathophysiology of the acute respiratory distress syndrome (ARDS) has been on the interaction between the lung, underlying causes of ARDS, and the role of white blood cells and platelets in contributing to lung injury. Given a lack of specific therapies for this common complication of critical illness, further insight into the pathophysiology of this syndrome is greatly needed to develop targeted interventions. The red blood cell (RBC) has been reported to undergo deleterious changes in critical illness and be present in the alveoli of patients with ARDS. Release of RBC contents is known to be injurious in other conditions but has only recently been studied in critical illness and ARDS. The contribution of the RBC to ARDS represents a new avenue of research that may produce new, targeted therapies for this deadly syndrome.