The goal of this study was to characterize asthma knowledge in high risk neighborhoods compared to a random sample of residents in the Chicago area. The Chicago Community Asthma Survey-32 (CCAS-32) was administered to 1006 Chicago-area residents and 388 residents in 4 high-risk Chicago inner-city neighborhoods. There was a significant difference in asthma knowledge between groups. The general Chicago-area respondents have an average desirable response rate of 71.6% versus 64.7% for respondents in high-risk communities (p < 0.0001). For some aspects of asthma knowledge, e.g., nocturnal cough, cockroach allergen, and vaporizer use, general knowledge was similarly low. For other aspects, such as the need for asymptomatic asthma visits and chest tightness, there were larger gaps between residents of high risk communities and the general community. High-risk neighborhoods in Chicago had lower asthma knowledge compared to the general Chicago community. This discrepancy may be contributing to the disparities seen in asthma morbidity. Public health efforts to increase asthma knowledge in these high risk minority communities may help reduce these disparities. Important misconceptions exist about asthma triggers, signs and symptoms, especially among lower income African American communities, that should be addressed by physicians.