The pathogenetic mechanisms leading to asthma are likely to be diverse, influenced by multiple genetic polymorphisms as well as elements of the environment. Recent data on the microbiome of the airway have revealed intriguing differences between the number and diversity of microbial populations in healthy persons and asthmatics. There is convincing evidence that early viral infections, particularly with human rhinovirus and respiratory syncytial virus, are often associated with the development of chronic asthma and with exacerbations. Recent studies suggest that two unrelated types of atypical bacteria, Mycoplasma pneumoniae (Mpn) and Chlamydia pneumoniae, are present in the airways of a substantial proportion of the population, bringing up the possibility that the persistent presence of the organism may contribute to the asthmatic phenotype in a subset of patients. This review will examine the current data regarding a possible role for infection in chronic asthma with a particular focus on atypical bacterial infections.