Heart disease and stroke continue to be the leading causes of death in the US. As a result, investigators continue to look for new and emerging biomarkers of disease risk. Because many of these emerging biomarkers are not as well documented as those of conventional lipid and lipoprotein risk factors, their value in clinical practice needs to be critically appraised and appropriate guidelines developed for their proposed use. The National Academy of Clinical Biochemistry (NACB) convened a multidisciplinary expert panel to develop laboratory medicine practice guidelines for a selected subset of these emerging risk factors as applied in a primary prevention setting of heart disease and stroke. The NACB expert panel selected lipoprotein subclasses and particle concentration, lipoprotein(a), apolipoproteins A-I and B, high sensitivity C-reactive protein (hsCRP), fibrinogen, white blood cell count, homocysteine, B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and markers of renal function as biomarkers that fell within the scope of these guidelines. Based on a thorough review of the published literature, only hsCRP met all of the stated criteria required for acceptance as a biomarker for risk assessment in primary prevention.