The pulmonary innate immune system has evolved over millions of years to provide swift detection of inhaled microbial agents and trigger well-balanced protective responses. Much more recent on the evolutionary scale is human activity, which has resulted in the release of a new class of potentially harmful, non-microbial compounds into the air. These xenobiotics include combustion by-products such as reactive oxygen species and polycyclic aromatic hydrocarbons. This review will summarize evidence showing how airborne xenobiotics can engage pulmonary innate immunity components at many levels. We will focus on potential effects of xenobiotics on airway dendritic cells, as these constitute key innate immune sensors in the lung, with the unique ability to initiate adaptive immunity. We propose that the aberrant processing of inhaled xenobiotics by an innate immune system that is now evolutionarily maladapted underlies the increase in chronic inflammatory lung diseases in modern times.