Ambient ozone has a significant impact on human health. We have made considerable progress in understanding the fundamental mechanisms that regulate the biological response to ozone. It is increasingly clear that genes of innate immunity play a central role in both infectious and noninfectious lung disease. The biological response to ambient ozone provides a clinically relevant environmental exposure that allows us to better understand the role of innate immunity in noninfectious airways disease. In this brief review, we focus on (1) specific cell types in the lung modified by ozone, (2) ozone and oxidative stress, (3) the relationship between genes of innate immunity and ozone, (4) the role of extracellular matrix in reactive airways disease, and (5) the effect of ozone on the adaptive immune system. We summarize recent advances in understanding the mechanisms that ozone contributes to environmental airways disease.