Stress and infections have long been independently associated with asthma pathogenesis and exacerbation. Prior research has focused on the effect of psychological stress on Th cells with particular relevance to atopic asthma. In this review, we propose new perspectives that integrate the role of infection in the relationship between psychological stress and asthma. We highlight the essential role of the mucosal epithelia of the airways in understanding the interaction between infections and the stress-asthma relationship. In addition, we review findings suggesting that psychological stress not only modulates immune processes, but also the pathogenic qualities of bacteria, with implications for the pathogenesis and exacerbation asthma.