The role of low-density lipoprotein cholesterol (LDL-C) in the pathogenesis of cardiovascular disease (CVD) and the clinical benefit of lowering LDL-C in high-risk patients is well established. What remains controversial is whether we are using the best measure(s) of LDL characteristics to identify all individuals who are at CVD risk or if they would benefit from specific therapies. Despite the successful LDL-C reduction trials, substantial numbers of patients continue to have clinical events in the treatment groups. The size of LDL particles and assessment of the number of LDL particles (LDL-Num) have been suggested as a more reliable method of atherogenicity. Each LDL particle has one apoprotein B-100 measure attached; therefore, determination of whole plasma apoprotein B can be considered the best measure of LDL-Num. Because the cholesterol content per LDL particle exhibits large interindividual variation, the information provided by LDL-C and LDL-Num is not equivalent. Individuals with the same level of LDL-C may have higher or lower numbers of LDL particles and, as a result, may differ in terms of absolute CVD risk. LDL particle size and number provide independent measures of atherogenicity and are strong predictors of CVD.