In this work we discuss the uncertainty in estimating the human health risk due to exposure to air pollution, including personal and population average exposure error, epidemiological designs and methods of analysis. Different epidemiological models may lead to very different conclusions for the same set of data. Thus, evaluation of the assumptions made and sensitivity analysis are necessary.Short-term health impact indicators may be calculated using concentration-response (C-R) functions. We discuss different methods to combine C-R function estimates from a given locale and time period with the larger body of evidence from other locales and periods and with the literature. A shrunken method is recommended to combine C-R function estimates from multiple-locales. This shrunken estimate includes information from the overall and the local estimates, and thus it characterizes the estimated excess of risk due to heterogeneity between the different locations.