There is need for the assessment of long-term effects of outdoor air pollution. In fact, a considerable part of the large amount of U.S. research money that has been dedicated to investigate effects of ambient particulate pollution should be invested to address long-term effects. Studies that follow the health status of large numbers of subjects across long periods of time (i.e., cohort studies) should be considered the key research approach to address these questions. However, these studies are time consuming and expensive. We propose efficient strategies to address these questions in less time. Apart from long-term continuation of the few ongoing air pollution cohort studies in the United States, data from large cohorts that were established decades ago may be efficiently used to assess cardiorespiratory effects and to target research on detection of the most susceptible subgroups in the population, which may be related to genetic, molecular, behavioral, societal, and/or environmental factors. This approach will be efficient only if the available air pollution monitoring data will be used to spatially model long-term outdoor pollution concentrations across a given country for each year with available pollution data. Such concentration maps will allow researchers to impute outdoor air pollution levels at any residential location, independent of the location of monitors. Exposure imputation may be based on residential location(s) of participants in long-standing cardiorespiratory cohort studies, which can be matched to pollutant levels using geographic information systems. As shown in European impact assessment studies, such maps may be derived relatively quickly.