The Genome Project has made it possible to assess the potential role of gene–environment interactions as determinants of asthma and allergies in a systematic way. Moreover, and contrary to what was the case during most of the twentieth century, the real limiting step today is the difficulty incomprehensibly assessing the degree and timing of environmental exposures. This article summarizes the theoretical basis on which to insert any studies of gene–environment interactions. It also outlines a specific example of such interactions, as represented by the role of genetic variations in the CD14 gene in relation to exposure to one of the ligands of CD14—namely, endotoxin.