Asthma is a chronic inflammatory disease of the lungs, characterized by airway hyperreactivity, mucus hypersecretion, and airflow obstruction. Despite recent advances, the genetic regulation of asthma pathogenesis is still largely unknown. Gene expression profiling techniques are well suited to study complex diseases and hold substantial promise for identifying novel genes and pathways in asthma; however, relatively few studies have been completed in human asthma. The few studies that have been done have identified many novel candidate genes and pathways in asthma pathogenesis, including ALOX15 and serine proteinase inhibitors cathepsin C and G. The interpretation of results of these studies should be cautious, as limitations include small sample sizes and heterogeneity of study populations and tissues sampled. In the future, the promise of gene expression studies would be enhanced by the use of larger sample sizes and attempts to standardize phenotype, sample collection techniques, and analysis. As the field of expression profiling in asthma advances, we hope it will improve our understanding of critical questions about mechanisms involved in susceptibility to the disease, as well as help to personalize care by improving appropriate selection of patients for prevention and treatment strategies.