Air pollution has been found to cause significant global mortality, with 6.8 million excess deaths attributed to air pollution each year, and similarly large numbers of exacerbations of asthma, chronic obstructive pulmonary disease, and cardiovascular diseases. Epidemiological research has identified associations, and experimental human exposure has provided critical information on dose–response relationships of adverse effects caused by controlled human exposure to individual pollutants. Human exposures further enable examination of the relationship of adverse effects such as symptoms and pulmonary function changes to presumed mechanisms of disease revealed through analysis of bronchoalveolar lavage fluid obtained from the lower respiratory tract. In this Perspective, we analyze the ethics of human exposure, the importance of the information gained, and the risks of such exposure. We find that these studies appear to have been done with proper approval of institutional review boards, were done with informed consent from the participants, and have rarely been associated with serious adverse events.