There is no FDA approved treatment for acute respiratory distress syndrome (ARDS), in spite of the relatively large number of patients with the diagnosis. In this report, we provide an overview of preclinical studies as well as a description of completed and future clinical trials in humans with ARDS. Preclinical studies dealing with acute lung injury (ALI) have suggested roles for complement and complement receptors, as well as the evolving role of histones, but details of these pathways are inadequately understood. Anti-inflammatory interventions have not been convincingly effective. Various cell growth factors are being considered for clinical study. Interventions to block complement activation or its products are under consideration. Stem cell therapies have shown efficacy in preclinical studies, which have motivated phase I/II trials in humans with ARDS.