A growing body of evidence from epidemiological and toxicological studies indicates a strong link between air pollution and cardiovascular morbidity and mortality. Many studies have focused on the role of single pollutants, but this report along with others indicates the importance of ambient air pollutant mixtures. This report utilizes two different air pollution mixtures to underline the importance of moving from a single-pollutant approach to a multi-pollutant approach: (1) photochemically-altered volatile organic compounds (VOCs), nitric oxide and nitrogen dioxide (NOx) and ozone (O3) and (2) concentrated ambient particles [CAPs, fine (PM[2.5]) and ultrafine (UFP)] and O3. In both studies the Langendorff cardiac perfusion model was used to access cardiac function. In these studies, mice demonstrated decreased cardiac function after multi-pollutant exposure, as indicated by decreased ventricular pressure and contractility. These two studies together help demonstrate the complexity of gaseous and particulate multi-pollutants and their adverse cardiovascular health effects.