The respiratory system is commonly known for being responsible for gaseous exchange. However, chronic exposure to air born pollution increases each year the number of asthma, chronic obstructive pulmonary disease (COPD), and lung cancer cases, which compels us to view the lung as a vulnerable organ due to the fact that because of its nature it enters in contact with substances present in the environment. Fortunately, the immune response mechanism acts locally in the lung in order to modulate the inflammatory response and to facilitate the clearance of inhaled pathogens, as well as volatile organic compounds (VOCs), metals, sulphur and nitrogen oxides, ozone and particulate matter (PM). Expanding our understanding of the molecular mechanisms underlying inflammation and pathology induced by airborne contaminant particles in the long term can help to develop strategies to reduce the risks of exposure to some of the most hazardous air pollutants, as well as to reduce the toxicity of nanomaterials and may also help to identify therapeutic targets to be used in the preventive treatment of susceptible groups.