Although genetic linkage and association studies have identified more than 25 asthma or allergy susceptibility loci, replication of significant results remains a problem. Moreover, these approaches typically ignore the true complexity of these diseases, such as the role of gene-by-environment and gene-by-gene interactions. As a result, many important associations might have been missed. Recent studies demonstrate not only that such interactions exist but also that the relationship between genotype and phenotype is more complex than previously thought.