The mortality of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain high despite advances in our knowledge and intensive care. This supports the contention that we need to further our understanding of the mediators that are involved in the pathogenesis of ARDS. The pathogenesis of ARDS proceeds as a continuum from exudation and inflammation to a fibroproliferative phase of diffuse alveolar damage. While a number of mediators are involved in the pathogenesis of ARDS, members of the CXC chemokine family have been determined to play a critical and pleiotropic role in promoting both recruitment of inflammatory cells, as well as in mediating aberrant vascular remodeling during both phases of ARDS. The importance of the biology of CXC chemokines in ALI/ARDS will be discussed in this review.