Global studies of the health impacts of fine particulate matter (PM2.5) have been based on particle mass, but there is evolving evidence indicating that adverse health effects can vary depending on the source and composition of PM2.5. This complicates the equitoxicity assumption commonly made regarding particle air pollution while raising the question as to which types of PM2.5 are most toxic. This report provides a comprehensive review of health effects of short- and long-term exposures to source-related components and trace constituents (specific markers of the individual sources) of fine particulate matter (PM2.5) in outdoor air pollution. The analysis evaluates the data and methods used, as well as the uncertainties in the underlying epidemiological studies, based on the relevant published literature. Most deaths attributed to outdoor PM2.5 air pollution (for example, by the Global Burden of Disease study) are caused by cardiovascular disease (CVD). The current evidence summarized in this report indicates that trace constituents from PM2.5 and PM2.5 mass from fossil-fuel combustion are among the greatest contributors to PM2.5 toxicity. Notably, PM2.5 from fossil-fuel combustion poses a larger cardiovascular disease risk per unit mass of PM2.5 than soil or biomass particles. Of the fossil-fuel combustion particles, coal- and traffic-related PM2.5 were found to be most consistently associated with cardiovascular mortality, especially due to ischemic heart disease (heart attacks) in both the short- and long-term exposure studies that were reviewed.