Low-density lipoproteins (LDLs) are susceptible to structural modifications by oxidation, particularly the small dense LDL particles. The formation of lipid peroxidation derivates, such as thiobarbituric reactive substances, conjugated dienes, lipid hydroperoxides, and aldehydes, is associated with changes in apolipoprotein conformation and affects the functional properties of LDLs. Oxidized LDL (oxLDL) formation in the subendothelial space of the arterial wall is a key initiating step in atherosclerosis because it contributes to foam cell generation, endothelial dysfunction, and inflammatory processes. In the last decade, immunoassays were developed using monoclonal antibodies against oxidation-dependent epitopes of LDL which made it possible to directly measure oxLDL in the circulation. Increased circulating oxLDL concentrations have been related to cardiovascular disease in some studies, although not always independently after adjustment of classical lipid markers. The Asklepios Study, investigating 2524 healthy middle-aged subjects, showed that circulating oxLDL is affected by many biological and lifestyle factors, as well as (generalized) subclinical atherosclerosis.