During and immediately after birth, neonates are exposed to an environment laden with bacteria, a stark contrast to the sterile environment of the womb. Over the ensuing weeks and months, environmental microbial communities colonize their new host, and subsequent host–microbial cross-talk provides key developmental signals for the host’s immune system. Emerging data from epidemiological and cellular research studies suggest that the nature of this cross-talk might be an underlying factor for the development, maintenance, and exacerbation of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease. This review describes recent findings concerning the bacterial microbiota in the airways and places these data within the context of epidemiological and experimental studies that allude to the functional significance of host–microbial cross-talk in pulmonary inflammation.