Asthma is a common but complex respiratory ailment; current data indicate that interaction of genetic and environmental factors lead to its clinical expression. In the United States, asthma prevalence, morbidity, and mortality vary widely among different Latino ethnic groups. The prevalence of asthma is highest in Puerto Ricans, intermediate in Dominicans and Cubans, and lowest in Mexicans and Central Americans. Independently, known socioeconomic, environmental, and genetic differences do not fully account for this observation. One potential explanation is that there may be unique and ethnic-specific gene–environment interactions that can differentially modify risk for asthma in Latino ethnic groups. These gene–environment interactions can be tested using genetic ancestry as a surrogate for genetic risk factors. Latinos are admixed and share varying proportions of African, Native American, and European ancestry. Most Latinos are unaware of their precise ancestry and report their ancestry based on the national origin of their family and their physical appearance. The unavailability of precise ancestry and the genetic complexity among Latinos may complicate asthma research studies in this population. On the other hand, precisely because of this rich mixture of ancestry, Latinos present a unique opportunity to disentangle the clinical, social, environmental, and genetic underpinnings of population differences in asthma prevalence, severity, and bronchodilator drug responsiveness.