The mass concentration of atmospheric particulate matter (PM) has been systematically used in epidemiological studies as an indicator of exposure to air pollutants, connecting PM concentrations with a wide variety of human health effects. However, these effects can be hardly explained by using one single parameter, especially because PM is formed by a complex mixture of chemicals. Current research has shown that many of these adverse health effects can be derived from the oxidative stress caused by the deposition of PM in the lungs. The oxidative potential (OP) of the PM, related to the presence of transition metals and organic compounds that can induce the production of reactive oxygen and nitrogen species (ROS/RNS), could be a parameter to evaluate these effects. Therefore, estimating the OP of atmospheric PM would allow us to evaluate and integrate the toxic potential of PM into a unique parameter, which is related to emission sources, size distribution and/or chemical composition. However, the association between PM and particle-induced toxicity is still largely unknown. In this commentary article, we analyze how this new paradigm could help to deal with some unanswered questions related to the impact of atmospheric PM over human health.