In an innovative scientific review in this issue, Grigoryev and colleagues report a method for choosing candidate genes for acute lung injury (ALI) based on gene expression data derived from multiple animal models of mechanical ventilation and shear stress. The authors conclude there are five key biologic processes that warrant further investigation: inflammatory and immune responses, cell proliferation, chemotaxis, and blood coagulation. This review represents an important first step toward studying the genetic epidemiology of ventilator-induced lung injury and ALI. The application of these findings to future human studies of the genetic influence on ALI risks and outcomes is discussed here.