Genetic studies of asthma have been plagued by a remarkable difficulty in constantly replicating results in different populations for most of the polymorphisms studied. This was true even when the quality of the study design and statistical power were not an issue. The most plausible explanation for these inconsistent results is that genetic polymorphisms, in most cases, do not directly influence risk for asthma but instead modulate the effect of environmental exposures on the inception and clinical expression of asthma and allergies. A better understanding of the genetics of asthma is thus inseparable from a better understanding of the mechanisms by which environmental factors increase the risk for asthma or protect against it.