Smoking is known to cause serious lung diseases including chronic bronchitis, chronic obstructive lung disease, obstruction of small airways, emphysema and cancer. Tobacco smoke is a complex chemical aerosol containing at least 8000 chemical constituents, either tobacco derived or added by tobacco product manufacturers. Identification of all of the toxic agents in tobacco smoke is challenging, and efforts to understand the mechanisms by which tobacco use causes disease will be informed by new biomarkers of exposure and harm. In 2009, President Obama signed into law the Family Smoking Prevention and Tobacco Control Act granting the US FDA the authority to regulate tobacco products to protect public health. This perspective article presents the background, rationale and strategy for using omics technologies to develop new biomarkers, which may be of interest to the FDA when implementing the Family Smoking Prevention and Tobacco Control Act.