When tissue damage and cell necrosis happen, histones are released into the extracellular environment, and become extracellular histones. Recent studies indicate that, extracellular histones are as dangerous signal molecules or inflammatory mediators, which play important roles in the development of acute respiratory distress syndrome (ARDS). In this review, we summarized recent researches on extracellular histones and ARDS, and elaborated the structures and functions of histones and the sources of extracellular histones, and investigated the possible mechanisms of the extracellular histones in ARDS and some potential measures for ARDS treatment targeting extracellular histones. Further studies on the relationship between extracellular histones and ARDS may provide theoretical basis and new therapeutic targets for ARDS treatment.