Air pollution is now considered the leading environmental cause of premature death worldwide. Recent results from cohort studies have made it possible to refine estimates of the risk of death associated with chronic exposure to fine particulate matter (PM2.5) in European and French populations. These new epidemiological findings were used to update the assessment of the impact of PM2.5 on mortality in mainland France. The quantitative health impact assessment method was applied to a model estimating annual average PM2.5 concentrations on a 2 × 2 km grid for the 2007–2008 period. The health benefits associated with various air quality improvement scenarios were calculated for metropolitan France for the 2007–2008 period. Anthropogenic pollution accounts for 9% of mortality in France, corresponding to 48,283 [95% CI: 17,527–74,426] attributable deaths per year. In urban areas with more than 100,000 inhabitants, on average, 15 [5–25] months of life expectancy at age 30 are lost due to PM2.5. The impact of PM2.5 is also significant in rural areas (an average loss of 9 [3–14] months of life expectancy). If all municipalities in mainland France were able to achieve the PM2.5 levels observed in the 5% least polluted municipalities within the same urbanization class, mortality could decrease by 7% and 9 [3–14] months of life expectancy could be gained on average, representing 34,517 [12,401–53,696] deaths avoided each year. If none of the municipalities exceeded the World Health Organization’s guideline value for PM2.5 (10 μg/m³), 17,712 [6,339–27,647] deaths could be prevented each year. Compliance with the 2020 European regulatory limit (20 μg/m³) could save 11 [4–17] lives per year. These results show that the various scenarios considered for reducing air pollution levels could result in significant health benefits.