Numerous epidemiological and toxicological studies have demonstrated the important role of secondary organic aerosol (SOA) in PM2.5-related adverse health effects. Primary organic aerosol, volatile organic compounds (VOCs), and intermediate volatile organic compounds (IVOCs) can react with multiple atmospheric oxidants (e.g., NOx and free radicals) and generate SOA. The chemical composition of SOA varies with precursor identity and aging conditions; however, knowledge regarding their transformation process and mechanisms and associated toxicity remains to be explored. Herein, this review systematically summarizes the chemical and toxicological transformations of different types of organic aerosols, i.e., fresh aerosols from different sources and representative precursors with different structures. Atmospheric aging generally enhances the toxicity of organic aerosol. Specifically, aged aerosols from biomass combustion and traffic emissions are more toxic than those from coal combustion, cooking, and biogenic sources, which might be attributable to their different precursor compositions. For certain precursors, aromatic compound-derived SOA always has the highest oxidative stress and toxicity, followed by unsaturated alkene and saturated alkane-derived SOA, which might be related with their different oxidation products. Furthermore, we describe the current research progress on the effects of major redox reactants involved in the aging process. The toxicity of SOA is complexly affected by the species and contents of atmospheric redox reactants, including 3C*(organic triplet oxidation state), NOx, and transition metal ions. This work is expected to provide a promising perspective for a better understanding of the toxicity profile of SOA and regulation of hazardous SOA pollution.