Asthma is a chronic inflammatory disease of the airways that is highly prevalent in the Western world. It is a genetically complex disease caused by multiple genetic and environmental factors, which may interact. Genetic research has recently incorporated environmental factors to investigate gene by environment interaction, and the first examples of gene by environment interaction in asthma have been reported. Linkage analyses indicate that one or more genes on chromosome 5q interact with environmental tobacco smoke in infancy in asthma development. Several candidate genes have been consistently shown to interact with the environment. These include the innate immunity genes CD14 and Toll-like receptor 4, and microbial exposures, as well as the detoxifying gene family glutathione-S-transferase and environmental tobacco smoke exposure and air pollutants. Gene by environment interaction is important in asthma pathogenesis, and future studies should take the interaction of both factors into account.