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Streptococcus pneumoniae (the pneumococcus) is the leading cause of pneumonia and bacterial meningitis. A number of recent studies indicate an association between the incidence of pneumococcal disease and exposure to air pollution. Although the epidemiological evidence is substantial, the underlying mechanisms by which the various components of air pollution (particulate matter and gases such as NO2 and SO2) can increase susceptibility to pneumococcal infection are less well understood. In this review, we summarize the various effects air pollution components have on pneumococcal pathogenesis and transmission; exposure to air pollution can enhance host susceptibility to pneumococcal colonization by impairing the mucociliary activity of the airway mucosa, reducing the function and production of key antimicrobial peptides, and upregulating an important pneumococcal adherence factor on respiratory epithelial cells. Air pollutant exposure can also impair the phagocytic killing ability of macrophages, permitting increased replication of S. pneumoniae. In addition, particulate matter has been shown to activate various extra- and intracellular receptors of airway epithelial cells, which may lead to increased proinflammatory cytokine production. This increases recruitment of innate immune cells, including macrophages and neutrophils. The inflammatory response that ensues may result in significant tissue damage, thereby increasing susceptibility to invasive disease, because it allows S. pneumoniae access to the underlying tissues and blood. This review provides an in-depth understanding of the interaction between air pollution and the pneumococcus, which has the potential to aid the development of novel treatments or alternative strategies to prevent disease, especially in areas with high concentrations of air pollution. [ABSTRACT FROM AUTHOR]