Fifty-nine million Americans (21% of the US population) live in rural areas of the United States. Compared with persons living in urban areas of the United States, rural populations have lower income, a higher rate of government versus private insurance, and decreased access to health care. Although there are reports of lower asthma prevalence in rural areas, the majority of these data have been published on international populations, with few available studies looking at American urban versus rural asthma prevalence on a national scale or comparing rural with nearby urban cohorts in the United States. A large body of literature, mainly generated from studies of rural Europe, suggests that lower prevalence might be due to beneficial effects of exposure to farm environments, but the extent to which this applies to the rural United States, where a smaller proportion of the population engages in farming, is unclear. The United States has the additional covariate of having a higher proportion of African Americans, who have a greater asthma burden than whites independent of socioeconomic status, clustered in cities. There are data indicating that rural patients have increased difficulty obtaining health care in general and limited data suggesting that they receive inferior care for asthma. Future work is needed to more clearly define asthma prevalence and morbidity among residents of the rural United States, as well as to identify interventions effective in this population.