Exposure to environmental contaminants has a profound effect on immune function, yet mechanistic understanding of how pollutants deregulate immune responses has, for many chemicals, remained elusive. Available data suggest that certain pollutants alter host immune responses and increase susceptibility to viral infection. In particular, data from a combination of epidemiological and animal studies show that exposure to dioxins, cigarette smoke, diesel exhaust and other air pollutants increase pathology associated with infection. Mechanistically, some of these chemicals disrupt the kinetics and efficacy of innate and adaptive responses to infection, whereas others influence viral latency. While there remain considerable gaps in our knowledge of the complex interactions between viruses, immune cells, and the host environment, these observations indicate that pollutants are important but overlooked contributors to susceptibility and pathogenesis of viral infections.