Despite being common and carrying an estimated mortality in excess of 30%,1 acute lung injury (ALI) remains poorly understood. Few recent developments have improved the clinical management of affected patients. Significant advances in understanding the epidemiology and pathogenesis of ALI have been increasingly reported over the past 20 years; however, there are currently no pharmacologic interventions for the syndrome. To date, lung protective mechanical ventilation stands as the sole intervention to improve outcomes.2 Only a fraction of patients exposed to predisposing environmental insults, such as sepsis or trauma, develop ALI, leading to the hypothesis that genetic variation is a significant contributor to ALI susceptibility and outcomes. Over the past decade, candidate gene approaches have suggested genetic associations related to immune system function and pulmonary permeability.3 This relatively new focus on genetic risk has the potential to elucidate novel pathways involved in the pathogenesis of ALI and contribute to personalized medicine by identifying subgroups of patients that could uniquely benefit from targeted therapy. This is particularly true as newer, larger-scale genetic approaches are applied to ALI.4,5 Despite these findings, the understanding of the genetics of ALI remains in its infancy relative to other diseases, even within pulmonary medicine. The nature of the syndrome as sporadic and requiring a significant environmental insult complicates family-linkage approaches, and its heterogeneity leads to challenges in targeting the correct population and replicating results.