This article summarizes the contributions of high-throughput genomic, proteomic, metabolomic, and gene expression investigations to the understanding of inherited or acquired risk for acute respiratory distress syndrome (ARDS). Although not yet widely applied to a complex trait like ARDS, these techniques are now routinely used to study a variety of disease states. Omic applications hold great promise for identifying novel factors that may contribute to ARDS pathophysiology or may be appropriate for further development as biomarkers or surrogates in clinical studies. Opportunities and challenges of different techniques are discussed, and examples of successful applications in non-ARDS fields are used to illustrate the potential use of each technique.