Feelings of hopelessness are prospectively associated with increased risk of death, progression of atherosclerosis and other health outcomes. Places as well as people may promote a sense of hopelessness. We used the Chicago Community Adult Health Study to investigate whether feelings of hopelessness cluster at the neighborhood level. Random-intercept logistic models were used to examine associations of hopelessness with neighborhood conditions (physical disorder and decay, perceived violence and disorder, social cohesion) and census-based measures of neighborhood socioeconomic conditions (poverty, unemployment, % high school dropouts) from 1980–2000. Of the 3074 participants, 459 were categorized as experiencing hopelessness. Greater physical disorder and perceived disorder and a higher unemployment rate were associated with increased odds of hopelessness. Individuals' reports of hopelessness reflect physical, socioeconomic, and opportunity characteristics of their neighborhoods above and beyond their individual characteristics. Changing opportunity structures in a neighborhood may play a key role in reducing individuals' feelings of hopelessness.