ALI/ARDS may be a particularly suitable disease process for gene-based therapies (Table 4 ). Th is is supported by increasing evidence from relevant preclinical ARDS models for the effi cacy of gene-based therapies that enhance or restore lung epithelial and/or endothelial cell function, strengthen lung defense mecha nisms against injury, speed resolution of infl ammation and infection, and enhance the repair process following ALI/ARDS. Despite this promising preclinical evidence, the potential for gene based approaches to ALI/ARDS in the clinical setting remains to be realized. Multiple barriers exist to the successful use of gene-based therapies in the lung, which limit the effi cacy of these approaches. Future research approaches should focus on overcoming these barriers, by developing more eff ective and less immunogenic vector delivery systems, developing strategies to focus gene expression on specifi c injury zones of the lung for defi ned time periods, and identifying better molecular targets that can take advantage of these potentially very powerful therapeutic approaches.