The concept of “exposome” has been introduced to allow an empowerment of environmental research, by improving measurements of external stressors and of internal biological changes, the latter taking advantage of advancements in high-throughput technologies called “omics.” Here, I discuss the application of the exposome concept and techniques to the field of air pollution. I address some open issues in air pollution science, such as the effects of components in a mixture, low doses, biological pathways, and a meaningful interpretation of omic findings in the context of “hallmarks” of disease. The exposome may represent the next frontier for the regulation of low-dose environmental contaminants.