Genetic variation provides the basis for differences in the host response to a variety of environmental factors that can result in complex genetic diseases, including asthma and atopy. Through our ability to capture genetic variation at the single-nucleotide level and our increasing ability to perform large-scale sequencing of the human genome, including the development of computer algorithms for improved data analysis, our understanding of these complex diseases has increased dramatically in recent years. The genetics of allergy have shifted from characterizing a single polymorphism in a candidate gene as being responsible for the disease to inclusion of a multitude of genetic and nongenetic risk factors. Studies now must consider complex relationships that modify an individual's susceptibility, including possible gene-environment and gene-gene interactions and possible epigenetic modification of the genome. This review will discuss the techniques used for genetic analysis of complex diseases, some of the important genes that have been replicated in multiple asthma studies, and the future of genetic studies in asthma.