Coronary heart disease (CHD), the leading cause of death in the western world, is multifactorial in nature. Abnormal lipoprotein levels are among the risk factors that cause atherosclerosis and, therefore, have been used as biochemical markers in assessing risk of developing CHD. The measurement of serum cholesterol, lipoprotein cholesterol, and apolipoproteins accurately and reliably has been hampered with technical difficulties. In addition, the interpretation of these tests and the determination of their clinical values have been challenging for both physicians and laboratory scientists. This article addresses and reviews the major current analytical and clinical concerns in the testing of lipids as well as the prevention and treatment of CHD.