Studies in both humans and mice clearly show that interleukin (IL)-13 is a central regulator of allergic inflammation. Numerous single nucleotide polymorphisms have been recently identified in the IL-13 gene and have been found to be associated with allergic and/or asthmatic phenotypes in different populations throughout the world. Furthermore, functional genomics studies are highlighting mechanistic pathways that may link genetic variation in IL-13 and disease. IL-13 is therefore an ideal model to study the impact of genetic variation on the regulation of gene expression and function in complex diseases.