Genetic research has revealed a number of asthma-susceptibility genes. In addition, with the development of genome-wide association studies, which has gained unprecedented momentum, the roles of many more candidate genes in asthma will be uncovered. In parallel with such genetic insight, a detailed understanding of the function of susceptibility genes in asthma is required, a task best suited for genetically tractable model organisms. The inherent limitations of models like the mouse necessitate finding complementary systems for study. Although the fruit fly Drosophila has not been used previously in asthma-related research, it might prove to be extremely helpful in relating genetic processes to biological function. We discuss the usefulness of the Drosophila model by analyzing potential homologs of known asthma-susceptibility genes in the fly. Except for those associated with adaptive immunity, we and others found unequivocal orthologs for all of them. Most asthma-related genes are indeed expressed in the airway epithelium. In addition, some are regulated upon airway infection of the Drosophila airway epithelium, pointing to an important role in airway immunity and development of asthma-like phenotypes in the fruit fly. Finally, high throughput functional analyses are needed to complete genome-wide comparison studies in complex diseases such as asthma. Because such studies are most readily performed in the fruit fly, it may be a particularly useful asthma model system.