The use of positional cloning for the identification of complex trait susceptibility genes has gained momentum with the completion of the human genome project. The approach involves the collection of well-phenotyped cohorts (either family-based or case–control designs), the generation of high-density single-nucleotide polymorphism linkage disequilibrium maps, and the application of powerful statistical methods to localize narrow regions of genetic association with disease. In 2003, two novel genes relating to asthma were identified using this approach, PHF11 and DPP10, neither of which had previously been implicated in the pathobiology of either asthma or allergy. In addition, further support for ADAM33 (the first asthma susceptibility gene identified by positional cloning) as an asthma gene was presented, although with mixed results. These discoveries open new avenues for research in asthma and allergy, and highlight the power (and limitations) of positional cloning for the identification of asthma genes, and complex trait genes in general.