For many years ozone was the most studied air pollutant, primarily because it caused acute, mostly respiratory, symptoms during “smog” episodes in Southern California that generated considerable public concern. In 1966, California enacted regulations requiring smog controls on cars to limit emissions that promoted the formation of ozone, before the Clean Air Act of 1970 led to the establishment of the U.S. Environmental Protection Agency (EPA). The Clean Air Act mandated the EPA to set National Ambient Air Quality Standards (NAAQS) to control the levels of pollutants that are considered harmful to public health based on a review of the scientific literature. Ozone was one of the initial so-called “criteria” pollutants for which NAAQS were promulgated, but these standards were based solely on adverse health effects related to short-term exposures. Over time, as accumulating evidence indicated that acute respiratory effects (airway inflammation and lung function decrements) occurred in people at lower and lower exposure concentrations, the NAAQS for ozone has been periodically modified, but the standard has always been a short-term standard and is currently 70 ppb over an 8-hour averaging time. The evidence for adverse health effects as a consequence of longterm exposure to ozone is much less robust than the evidence for effects of short-term exposures. The criteria pollutant for which there is strong evidence that long-term exposure is associated with a risk of premature mortality is particulate matter <10 mm in aerodynamic diameter (PM2.5) (1). That said, there is an increasing body of studies that report an increased risk of cardiopulmonary mortality in association with long-term exposure to ozone. Perhaps the first important study to report a mortality effect with long-term exposure was conducted by Jerrett and colleagues using data from the large (n= 448,850) American Cancer Society Cancer Prevention Study II (CPS-II) (2). The authors found a significant increase in the risk of death from respiratory causes associated with increased annual ozone concentrations. They were not able, however, to detect an effect of ozone on the risk of death from cardiovascular causes when they adjusted their analysis for concentrations of PM2.5. Subsequently, the analysis of this cohort was updated with a longer follow-up period and improved exposure estimates (3). The updated analysis confirmed the association of long-term ozone exposure with an increased risk of death owing to respiratory causes, but it also found an association with cardiovascular mortality that remained significant in a two-pollutant model that included PM2.5. In this issue of the Journal, Lim and colleagues (pp. 1022– 1031) report the results of another large study of long-term ozone and cause-specific mortality (4). The authors prospectively studied 548,780 participants in the NIH-AARP Diet and Health Study over 17 years of follow-up and found that the long-term annual average concentration of ozone was significantly associated with deaths due to cardiovascular disease (per 10 ppb; hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01–1.06), ischemic heart disease (HR, 1.06; 95% CI, 1.02–1.09), respiratory disease (HR, 1.04; 95% CI, 1.00–1.09), and chronic obstructive pulmonary disease (HR, 1.09; 95% CI, 1.03–1.15) in singlepollutant models. In models adjusting for coexposure to PM2.5 and NO2, these associations remained significant. The authors also found a significantly elevated respiratory disease mortality risk associated with long-term ozone exposure for NIH-AARP participants living in locations with warmer climates. The interaction with higher temperature is not really a surprise, as ozone concentrations increase as temperatures rise (5). Ozone is generated from motor vehicle emissions and other sources by photochemistry, so urban areas with warm, sunny afternoon weather after the morning rush hour (e.g., Denver, Houston, Las Vegas, Los Angeles, Philadelphia