Although low-density lipoprotein cholesterol (LDL-C) remains the primary target for coronary heart disease (CHD) prevention in the latest guidelines of the National Cholesterol Education Program, many individuals who have CHD do not have substantially elevated LDL-C but have derangement of other lipid fractions, most commonly low levels of high-density lipoprotein cholesterol (HDL-C). In the guidelines, HDL-C is important in risk stratification in primary prevention, influencing the need for and intensity of treatment of LDL-C, and both HDL-C and triglyceride are defined as risk factors for the metabolic syndrome, a secondary target of therapy. Triglyceride level also determines in which individuals non-HDL-C should be a secondary target of therapy. Risk assessment that takes into account the entire lipid profile will identify more high-risk individuals than evaluating LDL-C alone. Some epidemiologic data suggest that instead of measuring the cholesterol in LDL or HDL, measuring their respective apolipoproteins, apolipoprotein (apo) B-100 and apo A-I, may improve CHD risk assessment, and in some observational and interventional studies, ratios of lipids and/or apolipoproteins have been better predictors of CHD risk than levels of any one lipid fraction. Trials of lipid-modifying therapy also suggest that apolipoproteins and ratios may provide improved targets for therapy beyond LDL-C, but optimal values have not been established. Because lipid-modifying therapy affects multiple components of the lipid profile, the effect on all lipid parameters should be considered when selecting the most appropriate agent. Therapies with beneficial effects across the lipid profile would be expected to improve CHD risk reduction.