After almost 40 years of experience with the U.S. Clean Air Act (CAA), many of the original goals of the regulation have been achieved. The CAA and its subsequent amendments have been driven largely by science and technology, linking the Earth’s atmosphere with public health and welfare and sources of pollution. Knowledge in the 1960s about the atmosphere that influenced air pollution has been far surpassed by today’s knowledge. When the CAA was conceived, there was a philosophical recognition that we (humans) live within “one atmosphere.” In the 1970s, however, air pollution was separated into components based on the tenets of the law, which focused on perceived health effects of specific compounds or specific measurable quantities. As knowledge evolved beyond a perception of “inert” pollutants to urban photochemistry, regulation began to foresee certain positive and negative collateral effects of simple emission rollback strategies for pollution control. The complexity of atmospheric processes has led some to believe that the technical foundations of the CAA could be fundamentally flawed. Modernization, therefore, may be necessary to take account of today’s knowledge about the Earth’s atmosphere and the public’s risks of exposure to air contaminants.