The genetic susceptibility to the development of and variable outcomes in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has become a topic of great interest in the pulmonary and critical care community. Published studies of variable genetic susceptibility to ALI/ARDS already have identified some important candidate genes and potential gene-environment interactions. This article reviews these recent studies, features of the current approach, and implications for future prevention and treatment in ALI. The challenges and potential contributions of genetic epidemiology to the future prevention and treatment in ALI are discussed.