Over the last few years, a significant progress has been made in understanding of the genetic basis of asthma. This has led to the identification of several chromosomal regions and loci showing linkage to and association with asthma and asthma-linked phenotypes. Recent positional cloning approaches have also been informative in identifying several strong candidate genes for asthma. The next challenge will involve validation of these findings and, importantly, identification of the functional basis in the pathophysiology of asthma. This review will describe the power of positional cloning for the identification of asthma genes, highlight the functional importance of the genetic variants, and address the gene-gene and gene-environment interactions that are pertinent to this challenging field.