The striking racial and ethnic disparities in disease prevalence for common disorders, such as allergic asthma, cannot be explained entirely by environmental, social, cultural, or economic factors, and genetic factors should not be ignored. Unfortunately, genetic studies in underserved minorities are hampered by disagreements over the biologic construct of race and logistic issues, including admixture of different races and ethnicities. Current observations suggest that the frequency of high-risk variants in candidate genes can differ between African Americans, Puerto Ricans, and Mexican Americans, and this might contribute to the differences in disease prevalence. Maintenance of certain allelic variants in the population over time might reflect selective pressures in previous generations. For example, significant associations between markers in certain candidate genes (eg, STAT6, ADRB2, and IFNGR1) for traits such as high total IgE levels observed in resistance to extracellular parasitic disease in one population and atopic asthma in another supports the common disease/common variant model for disease. Herein is a discussion of how genetic variants might explain, at least in part, the marked disparities observed in risk to allergic asthma.