Air pollution is consistently linked with elevations in cardiovascular disease (CVD) and CVD-related mortality. Particulate matter (PM) is a critical factor in air pollution-associated CVD. PM forms in the air during the combustion of fuels as solid particles and liquid droplets and the sources of airborne PM range from dust and dirt to soot and smoke. The health impacts of PM inhalation are well documented. In the US, where CVD is already the leading cause of death, it is estimated that PM (PM < 2.5 μm in size) is responsible for nearly 200,000 premature deaths annually. Despite the public health data, definitive mechanisms underlying PM-associated CVD are elusive. However, evidence to-date implicates mechanisms involving oxidative stress, inflammation, metabolic dysfunction and dyslipidemia, contributing to vascular dysfunction and atherosclerosis, along with autonomic dysfunction and hypertension. For the benefit of susceptible individuals and individuals who live in areas where PM levels exceed the National Ambient Air Quality Standard, interventional strategies for mitigating PM-associated CVD are necessary. This review will highlight current state of knowledge with respect to mechanisms for PM-dependent CVD. Based upon these mechanisms, strategies for intervention will be outlined. Citing data from animal models and human subjects, these highlighted strategies include: 1) antioxidants, such as vitamins E and C, carnosine, sulforaphane and resveratrol, to reduce oxidative stress and systemic inflammation; 2) omega-3 fatty acids, to inhibit inflammation and autonomic dysfunction; 3) statins, to decrease cholesterol accumulation and inflammation; 4) melatonin, to regulate the immune-pineal axis and 5) metformin, to address PM-associated metabolic dysfunction. Each of these will be discussed with respect to its potential role in limiting PM-associated CVD.