Coronary heart disease (CHD) is the leading single cause of death in the United States and most Western countries, killing more than 400,000 Americans per year. Although CHD often manifests suddenly as a fatal myocardial infarction, the atherosclerosis that gives rise to the infarction develops gradually and can be markedly slowed or even reversed through pharmacological and lifestyle interventions. These same atherosclerotic processes also drive related vascular diseases such as stroke and peripheral artery disease, and individuals surviving occlusive events often develop additional complications including ischemic cardiomyopathy and heart failure. Therefore, better detection of subclinical atherosclerosis, along with more effective treatments, could significantly reduce the rate of death from CHD and related vascular diseases in the United States. In recent years, oxidation of polyunsaturated fatty acids (PUFAs) in plasma lipoproteins has been postulated to be a critical step in the development of atherosclerosis. If so, then monitoring lipid peroxidation should be a useful indicator of disease risk and progression. This review focuses on the evidence that specific PUFA peroxidation products, the F2-isoprostanes, are useful biomarkers that could potentially be utilized as indicators of CHD.