Air pollution is now considered the leading environmental cause of premature death worldwide. Recent findings from cohort studies have confirmed the existence of a risk of death associated with chronic exposure to fine particulate matter (PM2.5) among the European and French populations. These new epidemiological findings were combined with a high-resolution air quality modeling tool to assess the impact of PM2.5 on mortality in mainland France for the period 2007–2008. More than 48,000 deaths per year could be attributed to PM2.5, more than half of which occur in urban areas with over 100,000 inhabitants. If all French municipalities complied with the World Health Organization’s recommended limit (10 μg/m³), more than 17,000 deaths could be prevented each year in France. The average gain in life expectancy at age 30 would then be 4 months in France, but could reach more than one year in the most polluted municipalities. These results confirm that efforts continuing those implemented to date to improve air quality would result in a reduction in PM2.5-related mortality.